Annual Report 2014 Key Persons in CEHA

Center for Healthy Aging Annual Report 2014 Key persons in CEHA

Professor Assoc. Professor Professor Professor Professor Professor Lene Juel Rasmussen Astrid Jespersen Allan Krasnik Erik Lykke Mortensen Martin Lauritzen Ian D. Hickson Managing Director, Theme I Theme I Theme II Theme II Theme III Theme III

Assoc. Professor Professor Professor Professor Head of Hocine Mankouri Michael Kjær Vilhelm Bohr Thomas Söderqvist Administration Theme III Theme III Theme III Communication Tina Gottlieb and outreach

Center for Healthy Aging is supported by the Danish foundation Nordea-fonden 4 Involving research paves the way for healthy aging

7 Research, communication and outreach 7 Theme I: Community innovation for healthy aging 13 Theme II: Life course aging processes: Lifespan exposures and healthy aging 21 Theme III: Energy balance in humans: What are the mechanisms underlying reduced energy? 27 Selected intervention studies and cross-theme projects 2014 33 Communication and outreach platform

37 International recruitment in 2014

41 In memory of Associate Professor Lene Otto

45 Staff list

51 Internationalization and networking 53 IARU – International research cooperation 53 IARU – International congresses on Aging in Copenhagen 54 IARU – Graduate Student Conference 55 IARU – CEHA Summer School 55 iHAN – International Healthy Aging Network 57 Other international networking and events

59 Selected educational activities 61 PhD dissertations 62 PhD courses 62 Post graduate level 62 Master level 63 Pre graduate level 63 Other dissemination activities

65 Selected joint activities, grants and appointments 66 Joint activities 67 Major grants 68 Appointment

71 Management 73 CEHA Steering Committee 73 International Scientific Advisory Board 74 Internal Advisory Committee 74 CEHA Administration

75 Selected communication and outreach activities 77 Events 79 CEHA on social media 80 CEHA profile magazine 80 Book: The good senior life 80 Press activities

Annual Report 2014 · 3 Involving research paves the way for healthy aging

The desire to live a long, healthy life is not just part of ship of IARU, an alliance of ten of the strongest research- a speech at a christening party or a major birthday. For intensive universities in the world. In this way, we ensure most people, it is one of the fundamental parameters that our research is strongly anchored internationally. for a happy life. We also now know that it is precisely the combination of ‘long’ and ‘healthy’ that is critical New interdisciplinary themes because healthy aging means that it will not necessarily The results of the research we have achieved and the be accompanied by a large increase in the number of in- experience we have harvested since establishing CEHA firmities even though more and more birthdays pass by. in 2009 have been invaluable, and especially usable. The Healthy aging may be significant for the quality of life interdisciplinary research model is the Center’s hallmark for individuals but it is also a major factor at the com- and justification for its existence. This is why CEHA will munity level because there are indisputable advantages be developing its research model in coming years. A from having a healthy population; the healthier the new grant of a further 26 million USD from the Dan- population, the less pressure there is on welfare ser- ish Nordea-fonden has ensured that we shall be able to vices. Demographic trends with an increasing number of continue researching into a whole range of important elderly in Denmark and internationally have put healthy areas in coming years. aging at the top of national and international politi- Hitherto, work at the Center was split into six research cal agendas. Researching into how the population can columns which worked together on various projects. achieve healthy aging is therefore not just a task but very At CEHA, we are now building further on the experi- much also a necessity. ence harvested using this model and have established In recent years, the Center for Healthy Aging (CEHA) three themes that all incorporate the projects that were has been a significant player, not just nationally but also successful in the Center’s first period. At the same time, in international research into healthy aging. In coming whilst we shall also be launching a series of new projects. years, we shall continue to engage with the international community, also under the aegis of the EU, such The three themes are: as in the EIT Health KIC (see below for details) in which 1. Community innovation for healthy aging – CEHA research into healthy aging is attracting great attention, researchers investigate the significance of the local and by way of the University of Copenhagen’s member- community and opportunities for promoting the

4 · Annual Report 2014 and cover some important interdisciplinary problems to which we should like to find answers. At the same time, these interdisciplinary themes enable our highly specialized researchers to take entirely different methods of approach and thinking for the benefit of research. Interdisciplinarity means that we use electron microscopy and a cultural/historical helicopter approach in our research. We are not only interested in how aging occurs at the cellular level but also how psychological and social factors influence the possibilities for a good elderly life. Professor Lene Juel Rasmussen, Managing Director External involvement Our knowledge of a good elderly life is one of the many health and energy of the elderly in the last stage of reasons why we at CEHA will be seeking in coming years life. Much of this work is being done in collaboration to collaborate more with partners outside the University. with three different municipalities. Our researchers It is actually crucial for our research to be not only inter- are also engaged in studying how historical and social disciplinary but also involving, meaning that it interacts changes have influenced relations between people directly with those around us. An outside world that we and between generations. should very much like to get out into because, out of ne- 2. Life course aging processes: Lifespan exposures and cessity, we find we spend too long at a time in our ivory healthy aging – an area in which CEHA’s researchers tower. Much of CEHA’s research is done in dialogue with investigate the different factors that influence aging the people who are directly affected, that is citizens as processes throughout life, how citizens could be moti- well as all the professionals who are working to create a vated into active lifestyles and what happens to cells, good framework for citizens’ healthy aging. Municipali- muscles and the brain as we get older. Researchers ties are one of the natural collaborative partners for our are also carrying out a so-called intervention project research since they have political responsibility for many focusing on physical activity to protect against age- of the areas that affect healthy aging. Over the next five related changes in musculature and the brain. years, CEHA will therefore be participating in a series of 3. Energy balance in humans: What are the mechanisms intervention projects in municipalities, especially under underlying reduced energy? – a theme in which the aegis of the ‘Health promotional innovations ‘. We researchers focus on the body’s inability to repair cel- shall also be doing our utmost to regularly communicate lular damage and the mechanisms that cause the en- our results so that they can be quickly put into practice. ergy in our cells, and hence in our tissue and organs, In this way, we shall be satisfying one of our most to dwindle as we age. important goals: for CEHA’s research to get to work directly together with those it is all about – our citizens At CEHA, we feel that these are three themes in which who should hopefully live long, healthy lives. we can embrace research right from the cellular level via the individual to society and our culture, without doing less for one or the other. The critical factor is that we now have a range of issues that are well interconnected Professor Lene Juel Rasmussen, Managing Director

Annual Report 2014 · 5

Theme I Community innovation for healthy aging [Foto: Mand med røde seler – kommer snarest. Alternativt hænder fra iStock] Theme I

Community innovation for healthy aging

Group leaders goal is to achieve an understanding of the reality of Astrid Jespersen, Associate Professor healthy aging and to understand how healthy aging is Allan Krasnik, Professor promoted among aging citizens. Bjarke Oxlund, Associate Professor Susan Whyte, Professor Background and hypothesis The research in Theme I is guided by four research ques- Theme I is focused on community participation and local tions: practices as the foundation for healthy aging. We ex- 1. What processes contribute to changing cultural ideas amine how differences in local settings and practices, as about health and energy over the life course within well as in socio-economic position affect processes and socially contrasting communities? practices related to aging. Theme I researchers work in 2. In what ways does historical change affect social many disciplines, ranging from ethnology and anthro- relations between and within generations in a specific pology to public health, and work closely together on a society? range of research topics. In other words, Theme I’s aim is 3. How do different actors with diverse initiatives for to understand how the heterogeneity of local communi- healthy aging interact within a municipality? ties influences the promotion of health and energy of 4. With regard to healthy aging, how can relations aging citizens. between local stakeholders be reconfigured at the The research in Theme I is based on the close col- community level to promote energy for aging citizens laborations that we have established within four Danish nearing or in the late stages of the life course? municipalities: Ishøj, København, Vordingborg and Gentofte. These municipalities represent different organi- Theme I consists of cross-disciplinary and cross-faculty zational and institutional conditions as well as different research groups, which utilize a unique combination of population subgroups, as far as social class, ethnicity, age methods, including those from cultural history, cultural and health status is concerned. By focusing our research analysis, anthropology and public health. on these localities/municipalities, we create a common framework for projects and sub-projects, and facilitate Program performance insight into interactions between the bio-psycho-social, In 2014, we focused on establishing good working rela- organizational and technological dynamics and social tions and started fieldwork in all four municipalities. In energies during daily life within these communities. The addition, we recruited 1 senior researcher, 5 postdocs

Annual Report 2014 · 9 and 3 Ph.D.-students. The following paragraphs describe • Transferring healthy aging is the theme in a pro- currently active projects and sub-projects: ject based on the rise in public-private partnerships • The project on local practices of active aging inves- in health promotion, a trend where public health tigates the following three themes through ethno- agendas meet political aspirations of achieving future graphic fieldwork as well as policy analysis: Which life welfare by exporting Danish-developed welfare ideals are practiced through municipal active aging technologies and innovations. The project analyses policies? How is active aging transformed in local, the grounds for and effects of packaging and folding municipal practices? How is active aging packaged, Danish welfare into transferable objects able to travel formatted, commercialized and exported? to other destinations. • A project on intergenerational relations in age-related • The project on third sector governance aims to exam- transitions addresses the following questions through ine how local governments govern the ‘third sector’ ethnographic fieldwork: How are transitions from (public private co-production of services) – specifically work to retirement and age-influenced changes in privately run associations that target elderly individu- living arrangements experienced? How do aging als. The project maps financial setups and economic people navigate intergenerational relations, roles incentives used to support the collaborative arrange- and engagement? What effect do intergenerational ment between three local governments and the com- relations have on the older person’s health practices, munity associations that provide services to elderly. identity and experience of energy and resources? • A new project will evaluate whether follow-up home • Empowering community health is the subject of a visits could be a useful tool to improve care, secure cultural analysis of aging citizens’ practices of ‘health’ cross-sectoral coordination and to prevent re-admis- and ‘quality of life’ in a Danish municipality. This sion. The project analyses the use of follow-up home project asks the following questions: How do aging visits by general practitioners for older patients after people in Gentofte Municipality practice ‘health’ and discharge, and to what extent follow-up home visits ‘quality of life’ in their everyday lives? How do aging improve cross-sectoral care coordination. The project people’s subjective understandings of ‘health’ and also asks which patients (age, gender, diagnosis and ‘quality of life’ relate to their everyday lives? How do socioeconomic status) are receiving follow-up home interactions between individuals constitute different visits and whether the health trajectories are better forms of ‘community’? for patients who receive follow-up home visits than • The project on healthy aging among ethnic minorities for those who do not. is based on ethnographic fieldwork in Ishøj and sets • An anthropological postdoc project focuses on elderly, out to investigate the ways in which ‘healthy aging’ socially-isolated men on the eastern part of the island, and ‘the good life’ are created and enacted within Møn. Since the men may be difficult to contact, the the context of health promotion. This project targets postdoc has made it a key priority to develop the pro- ethnic minorities, and is expected to provide insight ject in collaboration with the staff at the local health into the effects of public health policy. care center. Through intensive ethnographic fieldwork • A project on negotiating needs, negotiating old age is among the elderly on the island, the post-doc project focusing on the introduction of ‘enabling care’ in the aims at discovering what causes social isolation context of Danish municipal eldercare. ‘Enabling care’ among elderly men and at finding ways to re-socialize is a new way of practicing eldercare, and a new way and engage the elderly men within their communi- of perceiving and attending to older people’s needs. ties. This project investigates how enabling care produces • Another anthropological study on aloneness takes knowledge about what ‘the good life’ involves for its point of departure from past fieldwork (carried older people, and what responsibility the welfare out in CEHA) among elderly Danish citizens receiving state has in ensuring it. home nursing. The project examines the significance

10 · Annual Report 2014 Theme I

of aloneness for health, wellbeing and social relations ported with decision aids for GPs and patients, and among the elderly. recognized in systems of care just like practices of drug prescription. This is not the case yet, but by In collaboration with colleagues from the Oxford Insti- understanding the existing processes of discontinuing, tute of Population Aging, we are also planning a new greater equality between prescribing, continuing and research proposal on problems and potentials related to discontinuing can be achieved. walkability of neighborhoods for the elderly. This project • The anthropological fieldwork – among elderly Danish is expected to yield significant insight into the relation- citizens receiving home nursing – and analysis rooted ship between physical and social activity and health in in citizenship studies focusing on rights, duties, and older people. responsibility, indicated that elderly citizens try hard to maintain their health by physical activities, training, Results eating nutritionally-balanced meals, and take medica- • Three political agendas are influential in how Danish tion as prescribed. municipalities work with promoting active aging in • A workshop was held to discuss the expectations local communities: The development and use of new and goals of the collaboration between with munici- welfare technologies; strengthening of the collabora- pal collaborators and Theme I. The workshop was tion with civil society organizations and lastly expan- attended by Theme I researchers, municipal col- sion of enabling care to encompass all older citizens laborators and a representative from the foundation in need of eldercare. Nordea-fonden. • A new form of rehabilitation referred to as enabling care has evolved during the last decade. Enabling care Conclusion refers to a certain rehabilitative mode of eldercare, Theme I research is carried out by a cross-disciplinary and in which older people receive training and guidance cross-faculty research group. This group is unique in its in regaining the ability to carry out practical every- ability to apply methods from cultural history, cultural day tasks and/or personal care through time-limited analysis, anthropology and public health. Our aim is home-based rehabilitation programmes. to identify how the heterogeneity of local communi- • Multiple and to some extend conflicting politi- ties influence the health and energy of aging citizens. cal agendas in the governance of pharmaceuticals During 2014, we began to collaborate with three Dan- in Denmark leaves it up to individual clinicians to ish municipalities, each with very different population navigate between the conflicting agendas. This in demographics and organizational character. Links with turn prompts clinicians to develop their own ways two additional municipalities are being developed, and of dealing with the friction between political objec- several new researchers have been recruited. Results tives, which can lead to unintended consequences of from completed projects have been published and a governance attempts. series of new projects have been initiated. It is expected • Healthcare agreements with specific content and with that Theme I projects will elucidate how local actors con- regular follow-up and systematic mechanisms for tribute to healthy aging for all citizens, and will explore organizing feedback between collaborative partners the impact of improved cooperation between municipal exemplify a useful tool for the coordination of health agencies, health professionals, businesses, associations, and social services, and document substantial im- and the citizens themselves. New Theme I projects are provements with the new health agreements in terms also exploring how historical and social change affect of formalizing a better coordination of the healthcare the relationships between and within generations in a system. specific social context. • The practice of discontinuation of drugs should be standardized, considered, well-researched, sup-

Annual Report 2014 · 11 Selected scientific publications PhD dissertations

Andersen JH, Whyte SR. Measuring risk, managing values: health tech- Andersen MC. A Question of Location – Life with Fatigue after Stroke, nology and subjectivity in Denmark. Anthropology & Medicine. DOI:10.1 CEHA Theme I, University of Copenhagen, January 2014. 080/13648470.2014.907022, 2014. Lassen AJ. Active ageing and the unmaking of old age: The knowledge Bødker M, Nielsen AJ. Providing rehabilitation online – invisible work and productions, everyday practices and policies of the good late life, CEHA diagnostic agents. Journal of Health Organization and Management. In Theme I, University of Copenhagen, September 2014. press. Ludvigsen B. Citizenship and Adaptation: Elderly people receiving home Kriegbaum M, Kildemoes HW, Rasmussen JN, Hendriksen C, Vass M, nursing: Perspectives on social relations, prevention, medicine and death, Mortensen EL, Osler M. Do Social background and intelligence early in CEHA Theme I, University of Copenhagen, May 2014. life influence use of coronary heart disease preventive medicine in adulthood? BMJ Open. 4:e004178, 2014. Nixon MS. Organising medication discontinuation: An explorative study of GPs’ decisions and practices when discontinuing statins, CEHA Theme Lassen AJ. Billiards, rhythms, collectives – Billiards at a Danish activity I, University of Copenhagen, October 2014. centre as a culturally specific form of active ageing.Ethnologia Europaea. 44:57-74, 2014. Rudkjøbing A. Towards coordinated care – Governance in a fragmented healthcare system, CEHA Theme I, University of Copenhagen, September Lassen AJ. Keeping disease at arm’s length: How older Danish people 2014. distance disease through active ageing. Ageing & Society. In press. Wadman S. Preventive tensions – Governing clinical research and treat- Lassen AJ, Moreira T. Unmaking old age – Political and cognitive formats ment practices in contemporary cardiovascular medicine in Denmark, of active ageing. Journal of Aging Studies. 30:33-46, 2014. CEHA Theme I, University of Copenhagen, August 2014.

Oxlund B, Whyte SR. Measuring and Managing Bodies in the Later Life Course. Journal of Population Ageing. 7: 217-230, 2014.

Rudkjøbing A, Strandberg-Larsen M, Vrangbaek K, Andersen JS, Krasnik A. Health care agreements as a tool for coordinating health and social services. International Journal of Integrated Care (exp. Publication De- cember 2014). In press.

Sander M, Oxlund B, Jespersen A, Krasnik A, Mortensen EL, Westendorp RGJ, Rasmussen LJ. The challenges of human population ageing. Age and Ageing. 0:1-3, 2014.

Wadmann S. Physician-industry collaboration: conflicts of interest and the imputation of motive. Social Studies of Science. 44:531–554, 2014.

A complete list of publications is available at healthyaging.ku.dk/publications

12 · Annual Report 2014 Theme II Life course aging processes: Lifespan exposures and healthy aging

Theme II

Life course aging processes: Lifespan exposures and healthy aging

Group leaders followed from age 50 to age 100 for the oldest surviving Erik Lykke Mortensen, Professor cohort members. Theme II researchers have also been in- Rikke Lund, Associate Professor volved in establishing the Danish Conscription Database Martin Lauritzen, Professor which includes draft board information on 728,160 men. Flemming Dela, Professor Background and hypotheses Introduction Life course exposures: Composite measurements of The maintenance of energy in the cells and tissues of adversities and risk factors as well as measurements of the human body is necessary for a continued active and positive environmental factors will predict individual healthy life. Life course exposures may influence aging differences in aging across major life periods: the earliest processes and the extent to which older individuals prenatal and early postnatal period, childhood, adoles- maintain energy and an active lifestyle, or lose energy cence and young adulthood, midlife and late midlife. and show pronounced decline in functional ability, cog- nition and an increased level of overall fatigue. Theme Age-related cognitive decline: Signs of progressive cogni- II tries to stimulate an energetic and active lifestyle in tive decline can be confirmed in a follow-up examination aging individuals by: of the 200 participants in the CEHA 2009-2013 cogni- 1) Investigating cohorts of the middle-aged followed tive neuroscience project and the results for this sample from their birth and coupling cognitive and physical can be confirmed in a larger sample of 600 subjects. function to exposures throughout their lifespan; 2) Investigating the metabolic profile of elderly individu- Physical activity intervention: Program adherence and als who receive preventive medication; and long-term beneficial effects will be greater for moderate 3) Testing interventions in the elderly with different levels training. We also hypothesize that the overall positive of physical fitness in order to study if interventions effects upon functional ability, cognitive functioning, can promote higher energy levels and a long-term health promotion and disease prevention will be greater post-interventional adherence to a physically active in the long-run for those using moderate physical train- and energetic lifestyle throughout old age. ing than those using a high intensity training regimen.

In addition, several Theme II researchers analyze data Cholesterol lowering drugs: It will be necessary to con- on the Glostrup 1914 cohort, a group of individuals duct interdisciplinary research to describe the complex-

Annual Report 2014 · 15 ity of a medical issue from biological, humanistic and use disorders, and age-related cognitive decline is being anthropological points of view. planned and will be initiated in 2015. An important area of aging research examines Program performance psychosocial risk factors for early aging measured as A major focus has been on life course social inequalities low grade inflammation (LGI), physical functioning and in early aging as reflected in low-grade inflammation allostatic load. Specifically, there is an interest in analyz- (LGI) and physical functioning in midlife. Data from the ing the association between stressful social relations Copenhagen Aging and Midlife Biobank (CAMB) form in private life and LGI as well as physical functioning. the basis for these projects as well as register linkage of Furthermore, the association between major life events the cohorts to the Danish Health and Social Registries and allostatic load has been investigated. All analyses including information from 1980 onwards. are based on data from the CAMB. Life course research- Associations between growth (birth weight, early ers are currently collaborating with several international adult and midlife BMI) over the life course and midlife researchers on projects based on CAMB data including, LGI, are also being investigated (CAMB). Based on data for example, Ivan Bautmanns from Vrije Universiteit in from Women’s Health Initiative the associations between Brussels who is investigating the association between education, income and prestige of occupation and LGI muscle endurance and self-perceived fatigue. are being investigated among older women. The Danish Intervention Study on Preventive Home Further studies of early physical growth and early Visits, including participants aged 75 or 80 years at base- behavioral milestones are based on the Copenhagen line, is investigating if the negative effect of mobility- Perinatal Cohort. Studies have been conducted on early related fatigue on subsequent mobility can be alleviated growth and behavioral milestones as predictors of adult by physical activity. personality and adult intelligence. Another major life course theme is health expectancy In addition to clinical studies of highly selected for those aged 50 and 65 between 2004-2010 in Den- participants, ongoing projects are analyzing the is- mark. An additional aim is to evaluate whether health sue of age-related changes in cognitive function in expectancy continues to increase more than life expec- both middle-aged (CAMB) and older populations (the tancy. Another project within this Theme is evaluating Glostrup 1914 cohort). One study is currently analyzing educational inequality in health expectancy before and the association between young adult intelligence and after the financial crisis in Denmark amongst 50 years physical performance in the middle-aged while another olds. Both projects are based on SHARE data study is focusing on associations between young adult (www.share-project.org). intelligence and risk of mental disorders. A first study Another major research focus in Theme II is cogni- based on the Danish Conscription Database is analyz- tive function. An important collaborative effort is the ing the association between intelligence at the conscript Glostrup neurocognitive clinical project. From 2009- board examination and cause-specific mortality in all 2013, about 200 men selected from the Metropolit Danish males born in the period 1939-59. Studies based cohort according to estimated change in cognitive on the Glostrup 1914 cohort have a major focus on the function were enrolled. The plan is to expand this project association between cognitive function in midlife and to a sample of about 600 participants. During 2014, the several health outcomes in old age such as dental health, continuation of the study was planned in detail and all decline in cognitive function, decline in physical function, necessary permissions obtained. The assessment will in- and all-cause mortality. Furthermore, a number of studies clude both neuropsychological assessment and MRI brain are analyzing the potential predictors of cognitive decline scanning. The same assessments will also be included in old age; these studies include analyses of occupation, in a new study which will be based on the Copenhagen leisure time activities and social relations as predictors of Perinatal Cohort and include both male and female cognitive decline. Finally, a large-scale study of associa- participants. tions between mental disorders, in particular alcohol

16 · Annual Report 2014 Theme II

Results mortality from both natural and unnatural causes. • CAMB has been completed and described in several • Social relations are associated with increased mortal- publications in the Journal of Aging and Health. ity risk among middle-aged men and women for a A conscription database comprising data on 728,160 variety of different social roles. Those outside the men has been completed and a paper describing the labor force and men seem especially vulnerable to this database has been published exposure. • The physical training intervention project has success- • Negative aspects of close social relations are associ- fully been initiated as a collaboration amongst several ated with a higher risk of ischaemic heart disease hos- research groups within the Center for Healthy Aging. pitalization. Conflicts with partner are not associated • A cohort of statin users for primary and secondary with higher risk. prevention purposes and matched controls has been • Mobility-related fatigue is not a significantly stronger established. risk factor for subsequent mobility limitations among • Patients with a diagnosis of Parkinson’s disease those with concomitant exposure to low socioeco- showed significant differences in morbidities early nomic status compared to those with a high socioeco- on, following, and prior to, their diagnosis, compared nomic status. with healthy controls. • Examination of the neurocognitive correlates of • Bariatric patients with type 2 diabetes had better decline in intelligence showed a global pattern of physical health related quality of life than non-diabet- impairment which was not indicative of accelerated ic patients. cognitive aging effects, or of mild cognitive impair- • Findings suggest that inactivity and training alter ment (MCI). mitochondrial biogenesis equally in young and elderly • The trajectory of intelligence from youth to late men. midlife was related to education, vocational train- • Both gender differences and social class gradients ing and certain health variables, although they did can be observed on physical performance tests in late not explain much of the variance in neurocognitive midlife. performance. • Social gradients in allostatic load can be observed in • The results indicate that intelligence may be more late midlife. amenable to life experience than previously thought, • Early life adversity may potentiate the effects of later and underscore the importance of identifying factors stress on cumulative physiological dysregulation. which may enhance or reduce the resilience to age- • Aspects of adult personality may be related to early related cognitive decline and neuropathology. postnatal growth. • Patients with stroke often suffer from sleep apnea • Intelligence may mediate associations between early which has a major impact on prognosis. socioeconomic position and adult personality. • Sleep changes may be strongly indicative of the later • The overall burden of cardiovascular risk factors may development of neurodegenerative disorders. be more important than individual risk factors for • The neurobiological basis for subclinical cognitive cognitive decline. decline in late midlife may include task-induced • No evidence was found for long-term effects of oc- deactivation alterations similar to the pattern seen in cupational characteristics on cognitive change in old patients with Alzheimer’s disease while mild cognitive age. impairment and task-induced deactivation reduction • No evidence was found that a higher level or mainte- may suggest an early marker for subtle cognitive nance of leisure activity was protective against cogni- decline. tive decline across a 10-year follow-up. • There is change in brain activation pattern in subjects • Cognitive ability and personality are related to a broad with loss of IQ since youth, even when this loss is range of socio-demographic variables in late midlife. subclinical. • Cognitive ability in young adulthood is related to • The change in brain activation pattern is not associ-

Annual Report 2014 · 17 ated with traditional risk factors for, or signs of, brain the establishment of the statin user cohort, the continu- ischemia. ation of the Glostrup neurocognitive project has been • The change in IQ from young adulthood to midlife is planned and a further clinical study including MRI is be- associated with educational attainment. ing planned and will be initiated during 2015. • Homocystein, which is a general risk factor for vascu- The basic assumption of the life course approach to lar disease, is also a determinant of brain perfusion in aging is that individual differences in aging, to a large elderly subjects. extent, can be explained by biological development and • Other determinants of brain perfusion were found to environmental exposures in childhood, adolescence and include hemoglobin, caffeine and blood CO2 levels. young adulthood. CEHA researchers have contributed evidence corroborating this general point of view, includ- Conclusions ing a number of studies focusing on the identification of Theme II researchers conduct observational epidemio- early aging biomarkers. These studies include several biological and clinical studies as well as intervention studies. logical markers (e.g., low-grade inflammation, telomere 2014 was very successful with number of significant length, mitochondrial function), physiological indicators results based on ongoing research as well as the success- (e.g., muscle strength, balance), cognitive decline, and ful initiation and planning of a series of new studies. In self-reported indicators of aging (e.g., disability, fatigue). addition to the physical training intervention study and The physical activity training intervention study is not

18 · Annual Report 2014 Theme II

only a substantial collaborative effort across the three Lund MT, Dalby S, Hartmann B, Helge J, Holst JJ, Dela F. The incretin CEHA Themes, but also an important example of CEHA effect does not differ in trained and untrained, young, healthy men. Acta Physiol (Oxf). 210:565-572, 2014. researchers moving from observational and experimental laboratory studies to naturalistic interventions contribut- Lund R, Christensen U, Kriegbaum M, Nilsson CJ, Rod N. Stressful social relations and mortality. A prospective cohort study. Journal of Epidemiol- ing to improving the health and quality of life of the ogy and Community Health. 68:720-7, 2014. present generations of older people. Wimmelmann CL, Smith E, Lund MT, Hansen M, Dela F, Mortensen EL. The psychological profile of bariatric patients with and without type-2 diabetes: Baseline results of the prospective GASMITO-PSYC study. Selected scientific publications Surgery for Obesity and Related Diseases. In press, 2014.

Dich N, Hansen AM, Avlund K, Lund R, Mortensen EL, Bruunsgaard H, A complete list of publications is available at Rod NH. Early life adversity potentiates the effects of later life stress on healthyaging.ku.dk/publications cumulative physiological dysregulation. Anxiety, Stress and Coping. 30: In press, 2014.

Gow AJ, Avlund K, Mortensen EL. Occupational characteristics and PhD dissertations cognitive aging in the Glostrup 1914 Cohort. Journal of Gerontology: Bay B. Assisted reproduction and child neurodevelopment, CEHA Theme Psychological Science. 69:228-236, 2014. II, University of Copenhagen, May 2014. Gram M, Vigelso A, Yokota T, Hansen CN, Helge JW, Hey-Mogensen M, Christiansen LB. Mitochondrial structure and function in feline hyper- Dela F. Two weeks of one-leg immobilization decreases skeletal muscle trophic cardiomyopathy: An animal model of spontaneous disease, CEHA respiratory capacity equally in young and elderly men. Exp Gerontol. Theme II, University of Copenhagen, December 2014. 58C:269-278, 2014.

Emme C. Quality of life in patients with chronic obstructive pulmonary Hansen M, Palsøe MK, Helge JW, Dela F. The Effect of Metformin on disease, CEHA Theme II, University of Copenhagen, February 2014. Glucose Homeostasis During Moderate Exercise. Diabetes Care. In press, 2014. Gram M. Mitochondrial function in young and elderly men after immobilization and aerobic retraining, CEHA Theme II, University of Copenha- Hansen NL, Lauritzen M, Mortensen EL, Osler M, Avlund K, Fagerlund B, gen, December 2014 Rostrup E. Subclinical Cognitive Decline in Middle-Age is Associated with Reduced Task-induced Deactivation of the Brain’s Default Mode Network. Hansen NL. The dynamic brain Activity patterns in cognitive ageing and Human Brain Mapping. 35:4488-4498, 2014. during cerebral blood flow modulation,CEHA Theme II, University of Copenhagen, November 2014. Hansen ÅM, Lund R, Bruunsgaard H, Rod NH, Garde AH, Molbo D, Av- lund K. Social Gradient in Allostatic load among Danish men and women Larsen S. Mitochondrial function in human skeletal muscle: Influence of in late midlife. Journal of Aging and Health. 26:72-87, 2014. age, physical fitness and insulin sensitivity,CEHA Theme II, University of Copenhagen, February 2014. Larsen S, Danielsen JH, Sondergard SD, Sogaard D, Vigelsoe A, Dybboe R, Skaaby S, Dela F, Helge JW. The effect of high-intensity training on Lund MT. The influence of lifestyle interventions on glucose homeostasis, mitochondrial fat oxidation in skeletal muscle and subcutaneous adipose CEHA Theme II, University of Copenhagen, September 2014. tissue. Scand J Med Sci Sports. In press, 2014.

Annual Report 2014 · 19 20 · Annual Report 2014 Theme III Energy balance in humans: What are the mechanisms underlying reduced energy?

Theme III

Energy balance in humans: What are the mechanisms underlying reduced energy?

Group leaders Background and Hypothesis Lene Juel Rasmussen, Professor I. Understanding the basic cellular mechanisms of aging Hocine Mankouri, Associate Professor/ At the cellular level, we aim to understand how DNA Ian Hickson, Professor damage contributes to aging. A number of DNA repair Michael Kjær, Professor pathways counteract DNA damage and are implicated Jørn Helge, Professor in suppressing premature aging and in maintaining Linda Bergersen, Professor genome stability in the nucleus and the mitochondria. Vilhelm Bohr, Professor The mitochondrion is known as the ‘powerhouse’ of Javier Pena-Diaz, Assistant Professor the cell, because they generate ATP, which is the fuel Andres Lopez-Contreras, Associate Professor for many intracellular processes. DNA repair pathways protect the nuclear and mitochondrial genomes from Introduction nearly continuous attack from intrinsic and external DNA Aging is associated with a general decline in energy damaging agents. Although cells can efficiently repair levels or ‘vitality’. At the cellular, tissue, and organ levels, DNA damage, if the rate of damage exceeds the rate of loss of vitality correlates with inability to adequately repair, mutations and other changes in genome struc- replace or repair ‘worn-out’ or damaged components. ture will eventually accumulate, leading to altered gene Theme III aims to better understand the molecular and expression, and cellular dysfunction. Indeed, increased physiological mechanisms that cause age-associated DNA damage and mitochondrial dysfunction are two loss of vitality. This knowledge will ultimately lead to the well-characterized phenotypes of aging. Furthermore, development of novel strategies to diagnose and coun- mitochondrial dysfunction leads to age-associated pa- teract age-associated functional decline, and allow us to thologies, such as cognitive and/or neurological decline, have a higher quality of life as we age, which can also be muscle weakness and fatigue. We believe that this described as ‘longer healthspan’. perpetual cycle of DNA damage and repair has important implications for understanding aging-associated changes in the physiology of cells and tissues. Theme III researchers study energy homeostasis/balance with a powerful Illustration: Lehninger Preparations by Odra Noel (odranoel.eu/). This piece is a homage to Lehninger, of the ‘Principles of Biochemistry’ set of tools, including molecular genetics, biochemistry, fame. It is part of the series of Homage to pioneers, made for an exhibi- molecular and cell biology, in the context of cell culture tion at the Oroboros Museum of Scientific Art in Innsbruck. and animal models, including mouse models. We are

Annual Report 2014 · 23 also investigating the effects of mitochondrial dysfunc- Program performance tion on organ/tissue level processes during aging, by I. Characterizing the cellular defects that contrib- analyzing the relationships between mitochondrial dys- ute to aging function, premature cognitive decline and age-associated Balanced levels of dNTPs are important for maintain- muscle dysfunction. ing genomic stability. We demonstrated previously that depletion of mtDNA in cultured human cells can lead to II. Understanding the relationships between cel- imbalanced cytosolic dNTP pools, and a corresponding lular aging & tissue/organ aging increase in chromosomal instability. The mtDNA carries Theme III researchers are investigating the connection genes that encode protein components of the electron between DNA damage and brain deterioration. Mito- transport chain (ETC) and proteins that facilitate ATP chondrial dysfunction leads to increased production production by oxidative phosphorylation. Mitochondrial of reactive oxygen species (ROS) as well as reduced proteins also perform de novo synthesis of pyrimidines production of ATP. The brain is especially susceptible to through dihydroorotate dehydrogenase (DHODHase), oxidative DNA damage from ROS, and this may directly which localizes to the inner mitochondrial membrane. contribute to age-associated cognitive decline and We demonstrated that inhibition of ATP synthase neurodegenerative diseases such as Alzheimer’s disease. or DHODHase decreases cytosolic dNTPs, leading to We therefore aim to better understand how cells repair increased DNA damage. These findings suggest that and respond to oxidative damage to the nuclear and mitochondrial dysfunction could directly (or indirectly) mitochondrial genomes. promote DNA damage and genome instability during aging. Theme III We are also examining how inherently ‘fragile’ or Theme III researchers are also investigating aging-asso- unstable regions of the human genome contribute to ciated decline in muscle function, a well-established but genome instability during aging. The RecQ family of poorly understood phenomenon. A contributing factor is DNA helicases appear to be critical in preventing age- physical inactivity, but other factors are decreasing capac- associated genome instability. We are further character- ity for muscle growth and relative increase in muscle ca- izing how the roles and mechanisms of these important tabolism (i.e., muscle breakdown) with age. In some indi- enzymes using a range of biochemical and cell biological viduals, the net effect is rapid muscle deterioration, also techniques. known as sarcopenia, whilst others are relatively resistant to muscle loss during periods of reduced physical activity. II. Characterization of novel biomarkers of vitality We are investigating the biological and physiological To identify novel biomarkers of vitality, we examined mechanisms that lead to, or could prevent muscle loss spontaneous DNA damage, cardiovascular risk and physi- and/or sarcopenia in the elderly. Better understanding cal performance in 2487 participants of the Metropolit of these mechanisms could potentially help us develop cohort (a birth cohort of 11, 532 men born in 1953 novel treatments or interventions that promote retention in the Copenhagen Metropolitan area). We observed of muscle mass in individuals susceptible to muscle loss that vitality correlates inversely with the abundance of during inactivity. In particular, we are examining how spontaneous DNA breaks, and correlates positively with physical training induces physiological change in muscle, several parameters of physical performance. The results and how this knowledge could be exploited to improve of this study reveal possible ‘early warning’ biomarkers ‘healthspan’ and vitality in older individuals, as well as in of incipient frailty or loss of vitality. Additional study of individuals whose capacity for physical training is limited these associations may ultimately provide novel insights and/or restricted for other reasons. into the physiological mechanisms that impact upon energy levels during aging.

24 · Annual Report 2014 Theme III

III. Characterizing the effects of physical exercise • Inhibition of ATP synthase or DHODHase results in a on sarcopenia subsequent decrease in cytosolic levels of dNTPs, and We investigated the properties of connective tissue in increased sensitivity to DNA damage. old and young athletes and non-athletes. The results • Mitochondrial dysfunction and increased levels of suggest that non-reversible advanced glycation end- DNA damage are potential predictors of cognitive products are present at a lower level in individuals who decline. perform endurance sports throughout their lives, even • Overexpression of DNA ligase III in mitochondria into old age. Although tendons tend to become ‘loose’ enhances cell survival following oxidative stress. after periods of inactivity, they can return to/ re-acquire • Subjective vitality is inversely correlated with spon- normal function and characteristics when activity is taneous DNA breaks, suggesting this could serve as resumed (i.e., during re-mobilization). Inactivity-related ‘early warning’ biomarker that is indicative of future change in mechanical properties of connective tissue loss of vitality. can be reversed by exogenous growth hormone, which • Persistent activation of the DNA damage response stimulate release of insulin-like growth factor I, especially protein, PARP1 causes the neurodegeneration seen in in younger individuals. the premature aging syndromes Cockayne syndrome We also demonstrated that muscle mass correlates (CS), ataxia telangiectasia (A-T), and xeroderma pig- inversely with the level of inflammatory markers in the mentosum A (XPA) diseases. blood. Interestingly, the level of inflammatory markers • High fat diet and supplementation with nicotinamide was similar in untrained but healthy young individuals adenine dinucleotide (NAD+) can alleviate some CS (≈20 yrs old) and highly-trained elderly endurance master phenotypes. athletes (70 yrs old). In normal older individuals who • The RecQ helicase, BLM, has a number of critical roles maintained a moderate level of activity, circulating in- in preserving genome integrity. Newly described roles flammatory factors were higher, muscle mass was lower, for BLM (and its orthologues in other organisms) and inactivity-induced muscle loss could be counteracted have been identified in promoting the resolution of markedly through use of anti-inflammatory medication. i) various secondary structures in replicating DNA, ii) homologous recombination repair intermediates, and Results iii) ultra-fine DNA bridges in anaphase. • Non-reversible advanced glycation end-products are present at a lower level in connective tissues of indi- Conclusions viduals who perform life-long endurance sports. At the cellular level, mitochondrial dysfunction and in- • The inactivity-induced changes in the mechanical herent chromosomal ‘fragility’ in the human genome can properties of muscles are counteracted by administra- contribute to age-associated increases in DNA damage tion of growth hormone in young individuals. and genome instability. Indeed, our recent observations • Skeletal muscle mass is inversely correlated with the reveal that increased levels of certain types of DNA dam- levels of inflammatory circulating markers, which are age may serve as a useful prognostic marker for loss of lower in endurance trained individuals, as compared vitality during aging. to untrained counterparts. During periods of inactiv- Physical activity leads to an array of physiological ity, the loss of skeletal muscle in elderly individuals changes, resulting in better muscle performance and is markedly reduced in participants receiving anti- increased vitality. Muscle mass and function deteriorates inflammatory medication. during periods of inactivity, and this can be counteracted • The age-related decline in number of muscle stem in some circumstances by exogenous growth hormone cells (‘satellite cells’) occurs independently of the level and/or anti-inflammatory medication. of physical activity undertaken.

Annual Report 2014 · 25 Selected scientific publications Thompson BA, Spurdle AB, Plazzer JP, Greenblatt M, Akagi K, Al-Mulla F, Bapat B, Bernstein I, Capella G, du Sart D, Fabre A, Farrell MP, Far- Bocquet, Bizard AH, Abdulrahman W, Larsen NB, Faty M, Cavadini I, Bun- rington S, Frayling I, Frebourg T, Goldgar D, Heinen CD, Holinski-Feder ker R, Kowalczykowski SC, Cejka P, Hickson ID, Thomä N. Structural and E, Kohonen-Corish M, Lagerstedt-Robinson K, Leung SY, Lindblom A, mechanistic insight into Holliday junction dissolution by topoisomerase Martins A, Moller P, Morak M, Nystrom M, Peltomaki P, Pineda M, Qi M, IIIa and RMI1. Nature Struct. Molec. Biol. 21:261-268, 2014. Ramesar R, Rasmussen LJ, Royer-Pokora B, Scott R, Sijmons R, Tavtigian S, Tops C, Weber T, Wijnen J, Woods M, on behalf of InSiGHT, Macrae Chatterjee S, Zagelbaum J, Savitsky P, Huttner D, Sturzenegger A, Janscak F, Genuardi M. Application of a five-tiered scheme for standardized clas- P, Hickson, ID, Gileadi O, Rothenberg E. Mechanistic insight into the sification of 2,392 unique mismatch repair gene variants lodged on the interaction of BLM helicase with intra-strand G-quadruplex structures. InSiGHT locus-specific database.Nature Genetics. 46:107-115, 2014. Nature Communications. 5:5556, 2014. A complete list of publications is available at Couppé C, Svensson RB, Kovanen V, Grosset JF, Karlsen A, Nielsen RH, healthyaging.ku.dk/publications Larsen J, Skovgaard D, Hansen M, Mackey A, Aagaard P, Kjær M, Mag- nusson SP. Life-long endurance running is associated with reduced glycation and mechanical stress in connective tissue. AGE. 36:9665, 2014. Doctoral dissertation

Fang EF, Scheibye-Knudsen M, Brace LE, Kassahun H, SenGupta T, Nilsen Larsen S. Mitochondrial function in human skeletal muscle: Influence of H, Mitchell JR, Croteau DL, Bohr VA. Defective Mitophagy in XPA via age, physical fitness and insulin sensitivity,CEHA Theme III, University of PARP-1 Hyperactivation and NAD+/SIRT1 Reduction. Cell. 157:882–896, Copenhagen, February 2014. 2014.

Larsen NB, Sass E, Suski C, Mankouri HW and Hickson ID. The E. coli Tus-Ter replication fork barrier causes site-specific DNA replication pertur- PhD dissertations bation in yeast. Nature Communications. 5:3574, 2014. Bieler T. Training of patients with hip arthrosis – the effect of strength Larsen S, Díez-Sánchez C, Rabøl R, Ara I, Dela F, Helge JW. Increased in- training and aerobic training, CEHA Theme III, University of Copenhagen, trinsic mitochondrial function in humans with mitochondrial haplogroup May 2014. H. Biochim Biophys Acta. 1837:226-231, 2014. Boesen A. Tendon and skeletal muscle responses to immobilization and Mackey AL, Karlsen A, Andersen JL, Couppé C, Mikkelsen UR, Nielsen rehabilitation in humans: Influence of aging and growth hormone admin- RH, Magnusson SP, Kjaer M. Differential regulation of the satellite cell istration, CEHA Theme III, University of Copenhagen, April 2014. density of type I and II fibres with lifelong endurance running in old men. Bursomanno S. Post-translational modification of proteins by SUMOyla- Acta Physiologica. 210:612-27, 2014. tion in response to DNA replication stress, CEHA Theme III, University of Maynard S, Keijzers G, Gram M, Desler C, Bendix L, Budtz-Jørgensen E, Copenhagen, October 2014. Molbo D, Croteau DL, Osler M, Stevsner T, Rasmussen LJ, Dela F, Avlund Christiansen LB. Mitochondrial structure and function in feline hyper- K, Bohr VA. Relationships between human vitality and mitochondrial res- trophic cardiomyopathy: An animal model of spontaneous disease, CEHA piratory parameters, reactive oxygen species and dNTP levels in peripheral Theme III, University of Copenhagen, December 2014. blood mononuclear cells. Aging. 5:850-864, 2014.

Gram M. Mitochondrial function in young and elderly men after immobi- Scheibye-Knudsen M, Mitchell SJ, Fang EF, Iyama T, Ward T, Wang J, lization and aerobic retraining, CEHA Theme III, University of Copenha- Dunn CA, Singh N, Veith S, Hasan-Olive M, Mangerich A, Wilson MA, gen, December 2014. Mattson MP, Bergersen LH, Cogger VC, Warren A, Le Couteur DG, Moaddel R, Wilson III DM, Croteau DL, de Cabo R, Bohr VA. A High-Fat Larsen NB. Analysis of site-specific DNA replication perturbation in eu- Diet and NAD+ Activate Sirt1 to Rescue Premature Aging in Cockayne karyotes, CEHA Theme III, University of Copenhagen. December 2014. Syndrome. Cell Metabolism. 20:840–855, 2014. Lund MT. The influence of lifestyle interventions on glucose homeostasis, CEHA Theme III, University of Copenhagen. September 2014.

26 · Annual Report 2014 Selected intervention studies and cross-theme projects 2014 Photo: Henrik Kristensen, Communication Consultant, Ubberup Højskole. Selected intervention studies and cross-theme projects 2014

LIFESTAT (Lead-PI Flemming Dela) ception of disease risk and the way risk of CVD is man- This is an interdisciplinary project that leverages ap- aged in the context of a patient’s daily life. In essence, proaches and knowledge from medicine, the humanities LIFESTAT investigates the complex interplay between and the social sciences to analyze the impact of statin medical knowledge, healthy behavior, life-style choices use on health, life-style and well-being in a cohort of and moral/medical imperative. Danish citizens. The impetus for the present project is the fact that more than 600,000 Danes are currently taking Targeted aims of LIFESTAT include: statins as a preventive treatment for cardiovascular dis- • Determine the biochemical and physiological pheno- ease (CVD). Statins are widely prescribed throughout the types of statin users with and without myalgia. developed world to lower blood cholesterol and reduce • Identify and characterize potential biochemical, CVD events and are generally well tolerated. However, physiological, lipidomic and metabolomic markers of through incompletely understood mechanisms, statins statin-induced myalgia. are reported to cause muscle pain (myalgia) in 20-30% • Analyze the relationships between economic, social, of users, and predominantly (up to 75%) in people who cultural and biological processes influencing percep- are physically active. This is counterproductive for health, tion of disease risk and compliance to CVD preven- because it reduces patient compliance in achieving target tion. levels of daily physical activity. The acceptable level of • Identify and characterize patterns of perceived CVD blood cholesterol and acceptable CVD risk are somewhat risk in statin users. arbitrary, and the typical patient receives knowledge on • Identify a typology of different beliefs about statins these and other health issues from a variety of sources. and behavioral practices. Although the pathways by which information flows to the patient and the patient’s perception of risk vary from In order to achieve this, a gathering of different research individual to individual, patterns may exist. The LIFESTAT disciplines is required. This project is also funded by the project will investigate the biological consequences of University of Copenhagen Excellence Programme for statin treatment of high blood cholesterol, patient per- Interdisciplinary Research. (UCHP2016).

Annual Report 2014 · 29 Photo: Henrik Kristensen, Communication Consultant, Ubberup Højskole.

Intervention project on physical activity The UBBERUP project (Lead-PI Jørn Helge) (Lead-PI Michael Kjær) The world-wide increasing prevalence of obesity is a The training intervention project is a collaboration combined effect of low compliance with daily goals among several research groups within the center. Re- for physical activity and high daily caloric intake, such cruitment, training and testing are carried out at clinical that average daily calories consumed exceeds average facilities at Bispebjerg Hospital (Kjaer group), and MRI daily calories burned. Weight loss can be achieved by a scans are conducted at Hvidovre Hospital (Siebner and change of life style, which includes daily participation Garde group). Finally questionnaires and a cognitive test in physical activity: this kind of life-style change often are administered by Lykke Mortensen and colleagues at requires participation in an intense, prolonged course the Department of Public Health (UCPH). The project has in life-style modification, under supervision. Many who been initiated and subjects (62-70 yrs old) are being re- enroll in such a course see immediate positive impact, cruited and randomized to 3 study subgroups, stratified including weight loss; however, the majority of partici- by intensity and type of training, as follows: pants fail to remain committed over the long term to a • Heavy resistance training 3x/week in a training center; change in life style, rapidly regaining lost weight after • Unsupervised moderate resistance training at home (2x/ the supervised intervention ends. week) and supervised 1x/week training at a hospital; This project will characterize the physiological fac- • Non-strenuous exercise activities (control group). Cur- tors that determine/influence an individual’s capacity to rent enrollment is 80 individuals. To date, compliance maintain weight loss and to change lifestyle after the with exercise regimens has been good, and relatively end of a prolonged lifestyle intervention. The study has few adverse effects of the exercise programs have been a cross-sectional (n=80) component and a longitudinal reported. Subject testing is proceeding on schedule. (n=80) component, and will be conducted at CEHA

30 · Annual Report 2014 and Ubberup College (Danish: højskole). Endpoints Book: The good senior life – a joint commu- monitored during the study include body composition, nication project (Lead-PIs Astrid Jespersen, aerobic fitness, capacity for fat oxidation, mitochondrial Rikke Lund, Lars Holm) function, inflammation, glucose metabolism etc. The CEHA researchers Associate Professors Astrid Jespersen societal impact of obesity is huge and reaching unprec- (Theme I), Rikke Lund (Theme II) and Lars Holm, (Theme edented levels. We strive to identify factors that lead to III), published a book entitled The good senior life – Find successful weight loss and lifestyle modification. Better the motivation and strengthen your muscles with exer- understanding of these factors will facilitate successful cise and protein consumption, through agreement with development of tailored interventions to promote long- Strandberg Publishing and assisted by CEHA Communi- term maintenance of healthy weight goals. cation and Press Officer Gitte Inselmann Frandsen. The book was published on 17 November, and by the end The IFAST project (Lead-PI Jørn Helge) of 2014, approximately 700 copies had been sold. The This study will investigate the effects of short-term book is inspired by both CEHA research and the UCPH intermittent fasting on insulin resistance (IFAST). During Excellence Programme for Interdisciplinary Research intermittent fasting, periods of fasting are alternated called CALM. It is about how older people can remain with periods of eating. Recent findings suggest that it active both physically and socially. Throughout the book has beneficial effects on glucose homeostasis even in we follow four case persons between 61 and 75 years. the absence of net weight loss. Here, a clinical study will CEHA researchers involved in the project wrote and explore the effects of intermittent fasting on glucose edited the book, which is also richly illustrated. Strand- metabolism in patients with type 2 diabetes. Possible berg Publishing launched the book at the year book fair mechanisms will be explored. Preliminary data shows BogForum at Bella Center, Copenhagen, where one of a high compliance to the intervention, a decrease in the authors, Lars Holm (Theme III), was interviewed by central obesity after the intervention and change in mito- the journalist Bente Dalsbæk in front of an audience, chondrial ADP sensitivity in skeletal muscle. The impact mostly +60 years old. The press work was managed in of the intervention on glucose homeostasis is not yet collaboration with Strandberg Publishing. By December, known. the book had been cited in more than 20 articles, including several long articles in national newspapers, and featured in two interviews on local television TV2. The highly acclaimed Danish webportal on Science Vidensk- ab.dk printed an excerpt of the book, focusing on social relations. Some of this information was also posted on Facebook and Twitter.

Annual Report 2014 · 31 32 · Annual Report 2014 Communication and outreach platform Communication and outreach platform

Group leader articles and highlights targeting health professionals, Thomas Söderqvist social workers, nursing home employees and other health professionals. Aim and focus in 2014 • Website: The CEHA website, currently being re-devel- CEHA is engaged in outreach activities designed to foster oped to feature reports on CEHA research, integrated interactions between the CEHA research community and with social media postings by CEHA researchers. Danish society at large. We want citizens, public authori- Newsletter: We are replacing the former newsletter ties and health professionals to engage with healthy aging with a continuous news flow as well as social media research and to learn more about the Center’s activities. presence on Facebook, targeting health professionals, We also want the public’s perspectives and experiences political decision-makers and the general public. to inform CEHAs vision for the future. The aim is to make CEHA the most valued and important source for news, 2) Dialogue-based communication discussion and opinion about healthy aging in Denmark. To build a dialogue-based communication platform using events and social media to promote dialogue between CEHAs outreach program has four major aims: citizens, professionals, politicians and researchers. These activities are managed by Hanne Boll Overgaard, MA, 1) Disseminate and Annika Holme, MA, management officer (Medical To disseminate CEHA research results via printed and Museion) and social media officer (Medical Museion), electronic mass media and on the internet via the CEHA respectively, since May 2014, whose management goals website. These activities are managed by Gitte Inselmann include: Frandsen, PhD, communication and press officer since • Events: A series of innovative events initiated in the February 2014 (CEHA, Communication Office, Faculty last quarter of 2014 involving CEHA researchers and of Health and Medical Science). Frandsen manages the community stakeholders. These events target the following tasks: non-professional general public. • Mass media dissemination for non-scientists: Press • Social media: We encourage CEHA researchers to releases and journalism in the print and electronic cultivate a social media presence, thereby promoting mass media, targeting broad segments of the Danish broad public engagement in issues related to healthy population. aging. To this end, the social media officer supports • Dissemination for health professionals: Specialized CEHA researchers and staff in the use of social media.

34 · Annual Report 2014 Professor Thomas Söderqvist

3) Interdisiplinary communication • Publications: ‘The good senior life’ To enhance the effectiveness and internal cohesiveness • Internet: Internet-based media presence nationally (identity) of the Center by strengthening interdisciplinary and internationally communication and dialogue among researchers in the Center through seminars and workshops. This task is the For more detail on activities, see pp. 77. responsibility of the Center management team. Conclusion 4) Awareness CEHA is unique among health research centers to have To increase awareness of CEHA and its brand within a strong communications and outreach program that Denmark and internationally; to improve networking at supplements traditional mass media dissemination with a national and international levels among aging researchers. strong focus on events and social media activities. So far we have fulfilled the milestones. The mass me- Thomas Söderqvist, director of the Medical Museion and dia dissemination activities are already up and running. a specialist in the public engagement with science, is the We need to gather more experiences before we make architect and head of CEHAs communication platform. any adjustments in the protocol and milestones. He supervises the practical aspects of CEHAs commu- We have spent the last half years planning the event nication activities, and has an active research program program and performing a number of very successful on the history and philosophy of healthy aging. Thomas events. It is too early to suggest any changes in the pro- Söderqvist oversees a course in cross-disciplinary science tocol and milestones. Likewise the social media program communication in the Masters Program in Public Health is also in the planning phase. Science, taught by postdoc Morten Hillgaard Bülow. Scientific publication Results Bülow MH, Söderqvist T. Successful ageing: A historical overview and In 2014, the communication program participated in critical analysis of a successful concept. J Aging Stud 31: 139-49, 2014. and/or promoted the following main activities: • Events: ‘Drawing Science’ and ‘Live Forever’ PhD dissertation • Events: ‘Welfare Innovation Day’ and ‘Science Slam’ Bülow MH, Unsettling successful ageing: A history and queering of the • Social Media: Increased activity on Facebook, Twitter concept of successful ageing in ageing research. University of Copenha- and Instagram gen, April 2014.

Annual Report 2014 · 35 36 · Annual Report 2014 International recruitment in 2014 International recruitment in 2014

Professor Linda Hildegard Bergersen part of a partnership to fight poverty-related diseases in Professor Linda Hildegard Bergersen was a guest profes- Africa. sor in CEHA until December 2013, at which time she During 2014, Professor Bergersen and one of her PhD was hired as a part-time professor. students, Mahdi Hasan Olive collaborated with Professor Professor Bergersen’s research is focused on regula- Vilhelm Bohr and Morten Scheibye-Knudsen in a project tion, function and transport of lactate and other mono- that explores use of a ketogenic diet to prevent or miti- carboylates in the brain in young and old animals and gate symptoms of Cockayne syndrome. humans. Professor Bergersen recently discovered that Professor Bergensen is also engaged in an ongoing a G-protein coupled lactate receptor, GPR81, is present collaboration with CEHA Managing Director Professor and active in brain (Lauritzen KH et al., 2014 Cereb Lene Juel Rasmussen and Professor Martin Lauritzen. Cortex). In 2014, Professor Bergersen recruited PhD This project is characterizing morphological and chemi- student, Elisabeth Holm Diget, who will be sponsored cal change at neural synapses in DNA repair-deficient by a three-year PhD student fellowship from the Danish transgenic mice. In another collaboration, Bergersen’s Lundbeck Foundation and who will participate in an postdoctoral fellow, Knut Husø Lauritzen is working with optogenetic study in collaboration with Karl Deisseroth Professor Rasmussen to analyze the role of mitochondrial (Stanford University, USA). Her doctoral project, entitled dysfunction in heart disease. Can optogenetic stimulation of G-protein-coupled recep- Professor Bergersen works closely with Professors tor 81 rescue cognitive decline? will use optogenetics Lene Juel Rasmussen (Theme III), Martin Lauritzen to investigate the physiological effects and molecular (Theme II) and CEHA associates Vilhelm Bohr and Albert mechanisms of GPR81. Gjedde. Bergersen, Shelton Mariga, Miriam Kolko and Albert Gjedde co-authored a perspective article entitled Lactate transport and receptor actions in cerebral malaria (Fron- Publications

tier of Neuroscience, May 2014). This article discusses Bergersen LH. Lactate transport and signaling in the brain: potential infection with plasmodium falciparum, a causative agent therapeutic targets and roles in body-brain interaction. J Cereb Blood in cerebral malaria, and new opportunities to develop Flow Metab. [Epub ahead of print], 2014

treatment or interventions to prevent this prevalent Bergersen LH, Eid T. Monocarboxylate transport matters. N Engl J Med. neurological disorder in tropical countries. The project is 371:1931-1932, 2014

38 · Annual Report 2014 Professor Linda Assistant Professor Hildegard Bergersen Javier Peña Diaz

Mariga ST, Kolko M, Gjedde A, Bergersen LH. Lactate transport and DNA repair in maintaining genome integrity, and DNA receptor actions in cerebral malaria. Front Neurosci. 19: 8:125 replication fidelity and in preventing human disease.

Lauritzen F, Eid T, Bergersen LH. Monocarboxylate transporters in tempo- Peña Diaz is also interested in instances when DNA repair ral lobe epilepsy: roles of lactate and ketogenic diet. Brain Struct Funct. enzymes introduce errors instead of removing them, also [Epub ahead of print] 2014 known as ‘error-prone’ DNA repair. In some circum- Rinholm JE, Bergersen LH. White matter lactate--does it matter? Neuro- stances, error-prone repair may ultimately have beneficial science. 2014 Sep 276:109-116, 2014 effects (for example, it may increase diversify within a

Lauritzen KH, Morland C, Puchades M, Holm-Hansen S, Hagelin EM, pool of antibodies), while in other circumstances, DNA Lauritzen F, Attramadal H, Storm-Mathisen J, Gjedde A, Bergersen LH. repair enzymes inadvertently promote disease-causing Lactate receptor sites link neurotransmission, neurovascular coupling, and mutations (for example, DNA repeat expansion leading brain energy metabolism. Cereb Cortex. 24:2784-2795, 2014 to progressive neurodegenerative disease). Peña Diaz is interested in the relationships between aberrant DNA repair, aging and brain disease, a good fit Assistant Professor Javier Peña Diaz in CEHAs molecular neuroscience group. In May 2013, Javier Peña Diaz (Assistant Professor) was Peña Diaz’s group includes two PhDs students, Sara recruited by CEHA to establish a research group in mo- Thornby Bak and Despoina Sakellariou. He is funded by lecular aging and neurobiology with focus on the role of CEHA, Department of Neuroscience and Pharmacology, DNA repair in aging-related disease. the Danish Cancer Society and the Danish Council of Peña Diaz obtained his PhD in molecular parasitology Independent Research. at the University of Granada working under the supervision of Dr. Dolores Gozalez-Pacanowska. Later he moved to the University of Trondheim, Norway under the super- Publication vision of professor Hans E. Krokan, and afterwards to the Bak ST, Sakellariou D, Pena-Diaz J. The dual nature of mismatch repair as University of Zurich, Switzerland under the supervision antimutator and mutator: for better or for worse. Frontier in Genetics. 5: of Dr. Pavel Janscak and Professor Josef Jiricny, where he 287, 2014. initiated his work on mechanisms of DNA repair in human disease. Peña Diaz’s current research is focused on the roles of

Annual Report 2014 · 39 Associate Professor Andres J Lopez-Contreras

Associate Professor Andrés J López-Contreras In September 2014, Andrés J López-Contreras established a new research group at the ICMM and joined CEHA. This group will study the impact of genomic instability on aging using transgenic mouse models. López-Contreras obtained his PhD in Biochemistry and Molecular Biology at the University of Murcia (Spain). Then, he moved to the Spanish National Center for Cancer Research (CNIO, Madrid), where he performed postdoctoral research under the supervision of Prof Fernandez-Capetillo. At the CNIO, López-Contreras generated several mouse models with alterations in genomic instability and characterized their susceptibility to cancer. López-Contreras’ current research goal is to understand the role of replication stress (RS) in normal aging exploiting transgenic mice with increased or decreased levels of RS. Proposed studies will evaluate long-term survival and will include proteomic analyses in vivo. His results could ultimately help identify novel biomarkers and/or clinically-relevant therapeutic targets. López-Contreras’ group includes 1 technician (Alexan- dra Avram), 1 PhD student (Eliene Albers) and 1 Postdoc- toral fellow (Mauro Sbroggiò), and is currently funded by the Danish National Research Program and the Danish Cancer Society.

40 · Annual Report 2014 In memory of Associate Professor Lene Otto

Annual Report 2014 · 41 42 · Annual Report 2014 In memory of Associate Professor Lene Otto

Lene Otto was an associate professor of ethnology from search, cultural inheritance, and the correlation between 2003 to 2013. From the beginning of her academic body, age and material culture. Lene Otto communicated career, Lene Otto worked to strengthen the connection the outcomes of her work through scholarly publication between ethnology and health research. Her thesis on and in the context of museum exhibitions. inter-disciplinary conferencing, published subsequently Over the years, Lene Otto served on many national as a book entitled Rask eller lykkelig (Healthy or For- and international honorary boards and committees, tunate), is widely read and used in academic courses editorial teams, and assessment committees. Her many on professional healthcare; the book is considered a professional activities reflected her serious commitment significant commentary on healthcare and welfare policy to the worlds of the academic science and museum in Denmark. curation. Lene Otto remained very active to the end of Given this background, it was natural for Lene Otto her life. Her work was and continues to be disseminated to take a leadership role in shaping CEHAs early research through radio programmes, reports and articles. in the area of humanistic aging, which was from the In her private life, even during her final illness, Lene outset anchored in the Faculty of Humanities at the Saxo Otto demonstrated unusual strength of will, a charac- Institute. Between 2009 and 2013, Lene Otto carried out teristic that also drove her commitment to excellence in ethnological and cultural/analytical research on aging, research. In older, lay illustrations of the process of hu- was the lead investigator in CEHA Program 5/Health in man ageing, the life course has often been represented Everyday Life, and was a member of the CEHA steering as a rising staircase ending at a high landing, followed group. by a descending staircase. Lene Otto, who passed at Lene Otto was energetic, industrious, serious and tar- the young age of 50, traversed up the staircase to the geted in her approach to research. Even after she fell ill, pinnacle of her life, never to descend from that pinnacle. she put health on the ethnological agenda and ethnol- We all feel great loss, in that Lene Otto’s life was too ogy on the health and disease prevention agenda. Her short. We all miss her as a colleague and friend, now other core interests were museology, material culture re- and always.

Annual Report 2014 · 43 44 · Annual Report 2014 Staff list Staff list

Complete staff list Merete Osler, Professor Paid by CEHA1 Hartwig Siebner, Professor Partly paid by CEHA2 Ulla Christensen, Associate Professor Not paid by CEHA Trine Flensborg-Madsen, Associate Professor Total Carsten Hendriksen, Associate Professor Paid or partly paid by CEHA: 71 persons Rikke Lund, Associate Professor Not paid by CEHA: 144 persons Charlotte Juul Nilsson, Associate Professor Anders Petersen, Associate Professor Definitions: Signe Vangkilde, Associate Professor 1 represents 1 person paid 1 full work year Helle Wallach Kildemoes, Assistant (37/hours per week in 12 months). Professor 2 represents 1 person paid part time in 1-12 months or full time in less than 12 month. Helle Bruunsgaard, Senior Researcher Ellen Garde, Senior Researcher Senior Researchers Egill Rostrup, Chief Physician Theme I Allan Krasnik, Professor Krisztina Benedek, Consultant Karsten Vrangbæk, Professor Birgitte Fagerlund, Consultant Susan Reynolds Whyte, Professor Niklas Rye Jørgensen, Consultant Astrid Pernille Jespersen, Associate Professor Theme III Linda Hildegard Bergersen, Professor Annegrete Juul Nielsen, Associate Vilhelm A. Bohr, Professor Professor Ian Hickson, Professor Bjarke Oxlund, Associate Professor Michael Kjaer, Professor Peter Magnusson, Professor Theme II Flemming Dela, Professor Lene Juel Rasmussen, Professor Åse Marie Hansen, Professor Nina Beyer, Associate Professor Poul Jennum, Professor Javier Pena Diaz, Associate Professor Martin Lauritzen, Professor Katja Heinemeier, Associate Professor Erik Lykke Mortensen, Professor Lars Holm, Associate Professor

46 · Annual Report 2014 Ying Liu, Associate Professor Pernilla Eliasson Andrés López-Contreras, Associate Diana Huttner Professor Maciej Kliszcak Abigail Mackey-Sennels, Associate Sheroy Minocherhomji Professor Anders Fabricius Nedergaard Hocine Mankouri, Associate Professor Søren Reitelseder Mansour Akbari, Assistant Professor Kata Sarlos Claus Desler, Assistant Professor Jesper Strickertsson Sasha Liberti, Assistant Professor Rene B. Svensson Jesper Løvind Andersen, Senior Yao Qi Researcher Peter Schjerling, Senior Researcher Across Theme II and III Therese Bieler Across Theme II and III Steen Larsen Jørn Wulff Helge, Professor Michael Taulo Lund Clara Prats, Associate Professor PhD Students Guest Researchers Theme I Michael Christian Andersen Theme I Tiago Moreira, Senior Researcher Marlene Bødker Amy Clotworthy Theme II Ivan Bautman, Professor Nanna Hilm Carlos de Mendes de Leon, Professor Aske Juul Lassen Alan Gow, Associate Professor Michael Simon Nixon Robert Fieo, Post Doc Sarah Wadmann Minna Mänty, Post Doc Theme II Stine Harrsen Bachkati Theme III Jeffrey Holmes, Professor Gunhild Tidemann Christensen Naja Liv Hansen Post docs Otto Henriksen Theme I Christian Scheele Elling Anna Horwitz Kamilla Pernille Nørtoft Johansen Rikke Hodal Meincke Margit Kriegbaum Gitte Lindeved Petersen Bodil Ludvigsen Laura Graves Ponsaing Henrik Hvenegaard Mikkelsen Laura Gertrud Sørensen Andreas Rudkjøbing Linda Waller Marielle Zoetmulder Theme II Sanne Barsballe Jessen Margit Kriegsbaum Theme III Jakob Agergaard Jolene Lee Masters Pedersen Aiste Aleliunaite Lene Rask Maria Angleys Iris Wiegand Sara Thornby Bak Rasmus Bechshøft Theme III Monika Bayer Victoria Bjerregaard Anna Bizard Sara Bursomanno Christian Couppe Kasper Dideriksen

Annual Report 2014 · 47 Jon Durhuus Across Theme II and III Nima Fakouri Anne Theil Gylling Jane Frederiksen Thomas Lau Hansen Bachelor/Master students Mette Flindt Heisterberg Andreas Herchenhan Theme III Ragna Djurhuus Signe W. Jørgensen Mark Lorenzen Nicolai Larsen Emilie Thomsen Cecilie Jæger Leidesdorff Dekang Liu Across Theme II and III Marya Morevati Carina Vestergård Abildskov Christian Nielsen Anne-Sofie Andersen Rie Harboe Nielsen Magnus Asping Annesofie Thorup Olesen Julie Hagstrøm Danielsen Özgun Ozer Sofie Greve Dideriksen Despoina Sakellariou Rie Dybboe Wei Wu Julie Mucha Økjær Jørgensen Ronni Sahl Across Theme II and III Camilla Skovborg Liselotte Bruun Christiansen Stine Dam Søndergaard Tine Lovsø Dohlmann Caroline Wiuff Christian Eriksen Martin Gram Pregraduate Research Students Andreas Vigelsø Hansen Theme III Kristine Bramsen Andersen Merethe Hansen Maren Høgberget Sune Dandanell Jørgensen Jonas Frimer Kristiansen Marianne Kristensen Mads Rohde Loeb Anja Birk Kuhlman Nikolaj M. Malmgaard-Clausen Malene Kristensen Maag Mathias Bech Møller Thomas Morville Frederik Scheel Stinna Skaaby Ditte Søgaard Across Theme II and III Andreas Ziegler Monika Calov Kirstine Kjær Christensen Research Assistants Marie Dehlbæk Theme I Malene Bødker Arthur Ingersen Aske Juul Lassen Sofie Drevsholt Jørgensen Anne Line Jørgensen Theme II Kjeld Andersen Kasper Bøgh Kristensen Emilie Just-Østergaard Malene Glerup Nielsen Kristian Klinkby Charlotte Boslev Præst Marie Grønkjær Pedersen Cathrine Scheuer Mimmi Torp

48 · Annual Report 2014 Lab Technicians Communication and outreach platform Theme II Micael Lønstrup Morten Hillgaard Bülow, Post doc Gitte Inselmann Frandsen, Communi- Theme III Alexandra Avram cation and Press Officer Anne Marie Bundgaard Annika Holme, Social Media Curator Malgorzeta Clausen Hanne Boll Overgaard, Event Curator Kenneth Jakobsen Bente Vinge Pedersen, Head of Section Anja Sisko Jokipii-Utzon Thomas Söderqvist, Professor Ann-Christine Ronnie Reimann Ann-Marie Sedstrøm CEHA administration Camilla Brink Sørensen Tina Gottlieb, Head of Administration Theresa Wass Line Damberg, Academic Officer Ditte Marie Hansen, Student Assistant Across Theme II and III Julie Roll, Student Assistant Jeppe Bach Thomas Tjærandsen, Student Assistant Thomas Beck Regitze Kraunsøe Katrine Qvist

Secretaries Theme I Mads Christoffersen Emil Bjarne Johansen Jonas Møller Pedersen

Theme II Eva Jepsen

Theme III Elin Erichsen Birgitte Kjær Else Pedersen

Across Theme II and III Jacqueline van Hall

Other Theme I Janne Sørensen, Research Coordinator

Theme II Lykke Kempfner, PhD Drude Molbo, Database Manager

Across Theme II and III Christina Neigaard Hansen, Molecular Biologist Søren Lindemose, Molecular Biologist

Annual Report 2014 · 49 50 · Annual Report 2014 Internationalization and networking Summer school student speaks intensely with a resident of Søndervang. Photo: Lizette Kabré. Internationalization and networking

IARU – International research cooperation Committee members that the next IARU ALH Graduate From the outset, CEHA has been closely associated with Student Conference would take place in 2016 in Tokyo, the International Alliance of Research Universities (IARU), Japan. a prestigious alliance that includes the University of Co- penhagen. The other IARU members are Yale University, The ALH Steering Committee members are: University of California at Berkeley, Swiss Federal Institute • Prof. Barry Halliwell, National University of Singapore of Technology in Zurich (ETH), University of Cambridge, • Prof. Kaarin Anstey, Australian National University University of Oxford, National University of Singapore, • Prof. Xiaoying Zheng, Peking University Australian National University, Peking University and the • Prof. Junichiro Okata, University of Tokyo University of Tokyo. IARU is a valuable networking op- • Prof. William Satariano, University of California, portunity for members of CEHA, who arrange meetings Berkeley and workshops and utilize IARU as a mechanism for • Dr Louise Lafortune, University of Cambridge enhancing collaboration and future research activities, • Prof. Sarah Harper, University of Oxford mainly through the IARU Aging, Longevity and Health • Prof. Michael Ristow, ETH (ALH) initiative. • Prof. Lene Juel Rasmussen, University of Copenhagen The close association between CEHA and IARU is a cornerstone in the efforts to internationalize CEHA. In Detailed information on IARU ALH can be found at 2014, CEHA empowered IARU network further by form- www.iaruni.org/research-initiatives/aging. ing the ALH Steering Committee, whose raison d’être is to increase engagement across IARU campuses and to promote joint activities and funding opportunities for IARU – International congresses on Aging in IARU ALH participants. Copenhagen The first meeting of the IARU ALH Steering Com- In June 2014 in the Copenhagen area, two IARU ALH mittee was held on 20 June 2014. At this meeting, the conferences were sponsored by University of Copen- Committee agreed on Terms of Reference and discussed hagen and CEHA. The 2nd IARU ALH Graduate Student new opportunities of mutual interest, such as a recipro- Conference on aging also took place, so that ALH gradu- cal exchange PhD program/fellowship, collaborative ate students could benefit most from the overlapping research projects, and a biennial IARU ALH Graduate conferences. Student Conference. It was agreed among ALH Steering As noted at these conferences, the ongoing rapid

Annual Report 2014 · 53 GDN5 participants (June, 2014, Marienlyst, DK) CHA participants (June, 2014, Copenhagen, DK)

increase in the mean age of human populations and the University, Peking University, National University of mechanism(s) of human aging are ‘hot topics’ of the day, Singapore, Australian National University, University of being investigated in many diverse studies in research California, Berkeley, University of Tokyo and University of institutions worldwide. University of Copenhagen and Copenhagen). CEHA are heavily engaged in aging research, some of GDN5 focused on the genetic and biomolecular which involves collaborations with its IARU partner uni- mechanisms of genome instability and neurodegenera- versities. tive disease in the context of human aging. Leading-edge aging research must leverage expertise The conferences were attended by expert researchers from many distinct disciplines and seeks to fulfill the from IARU and non-IARU universities and were both or- following goals: 1) to address the implications of popula- ganized by CEHA, University of Copenhagen. GDN5 was tion aging within social, cultural, psychological, eco- co-organized by CEHA and the GDN organizing commit- nomic, political and public health contexts; 2) to define tee. and understand the molecular biological and physiologi- A commentary article on CHA will be published in cal bases of human aging; and 3) to identify factors that the March 2015 issue of Age and Aging available online: protect or promote aging-related disease and dysfunc- ageing.oxfordjournals.org/content/early/2014/12/01/age- tion. ing.afu189.full.pdf These issues were discussed, and nearly 70 lectures A summary of key points and emerging issues from and 10 posters were presented, at two IARU conferences CHA and GDN5 and both conference programs can be in Copenhagen: accessed online at healthyaging.ku.dk/activities/iaru- • Cultures of Health and Aging (CHA), 20-21 June, congress-2014. 2014 • Genome Dynamics in Neuroscience and Aging 5 (GDN5), 17-20 June, 2014 IARU – Graduate Student Conference The 2nd IARU ALH Graduate Student Conference, organ- CHA focused on population aging and the challenges it ized by CEHA Network for Young Scholars, was held in presents to human society. It included a session enti- Copenhagen, immediately following the CHA confer- tled Aging in a National and International Perspective, ence: where researchers from seven IARU universities provided • Aging Research and Scientific Careers,21-22 June, country-specific perspective on aging issues (Oxford 2014

54 · Annual Report 2014 Participants: IARU Graduate Student Conference Aging Research and Scientific Careers (June, 2014, Copenhagen, DK)

Twenty-one students from IARU partner universities insight into the lives of older people in Denmark. During participated and networked during the conference dis- the visit, the students interacted one-on-one with the cussing diverse topics, such as: Theories of aging – How residents of Søndervang. Both students and residents do we understand aging?, Studies of aging and behav- reported that this interaction was valuable and mutually ior, Health care services among the general population beneficial. and The physiology of health and aging – from cell to society. Conference participants also spent a full day at iHAN – International Healthy Aging Network the Euroscience Open Forum 2014 – Science Building The International Healthy Aging Network (iHAN) is part Bridges, during which students participated in career of IARU. The researchers in iHan collaborate to study related activities, such as Career Track for Young scientist molecular and cognitive biomarkers of healthy aging (esof2014.org). (Also see p. 77). and age-related diseases, including type 2 diabetes and Alzheimer’s disease. iHAN members include research- IARU – CEHA Summer School ers from University of Melbourne, Australia National CEHA hosted the 4th interdisciplinary Summer School University, Queensland University, Yale, Johns Hopkins on Interdisciplinary Aspects of Healthy Aging, 2-21 July, University, University of California, Berkeley, McGill, 2014 at UCPH, Copenhagen. University of Oslo, University of Aarhus, and University of The Summer School gives students the opportunity Copenhagen. to learn and use research methods from other disciplines, and to develop new projects with guidance from Seminars, meetings, symposia Summer School teachers. CEHA Associate Professor In February 2014, iHAN hosted a seminar entitled Be- Ying Liu has developed and implemented the Scientific yond the Amyloid Cascade arranged by Professor Albert Programmes, which also included international lectur- Gjedde at John Hopkins University. The network also ers. Prof. George Leeson, University of Oxford, a visiting hosted a mini-symposium in July 2014 entitled Alzhei- scientist at CEHA, gave lectures to students at the 2014 mer’s disease: mechanisms, diagnosis and prognosis, at Summer School. the BRAINlab of the University of Copenhagen. Summer School students were from Yale, Peking Uni- Professors Albert Gjedde, Ron Kupers and Maurice versity, University of Oxford, University of Tokyo, Austral- Ptito (University of Copenhagen), met with Professor ian National University, National University of Singapore, Robin Alexander, Dr. Charles Rupprecht, and Professor University of Copenhagen, Universidad de Federal de Arve Lee Willingham at Ross University School of Veteri- São Carlos, Brazil, and the University of Tohoku, Japan. nary Medicine, on the island of St. Kitts, in May 2014. As a new initiative, students visited the home care The goal of this meeting was to establish a collaborative facility Søndervang in Copenhagen, in order to gain project using positron emission tomography (PET) tech-

Annual Report 2014 · 55 Figure 1 A: Example of resting-state and task-evoked fMRI. B: Forepaw stimulated fMRI analysis. Forepaw stimulation (2 mA, 9 Hz, 0.3 ms) for 30 s revealed BOLD signal increases in S1FL (somatosensory forelimb) and VPL (ventral posterior lateral part of the thalamus) across several slices. BOLD time course of S1FL. BOLD scale % change. Source: BGra- toct22 Exp #22. Acquired during visit of iHAN member Fahmeed Hyder to BRAINlab at Panum Institute in October 2014.

nology. This project will support future research on aging visits, and the feasibility of performing in vivo (rat brain) in non-human primates using PET technology. and ex vivo (Guinea pig brain, primate brain) studies Drs. Anders Rodell and Michael Gejl represented iHAN with this technology was demonstrated. See Figure 1 for at the Symposium of the Australian Society for Molecular representative images collected during these collabora- Imaging at the Center for Advanced Imaging in Brisbane, tive visits. Australia, in July 2014. In 2014, Professor William Jagust hosted Adjmal Nahimi (MD) at the University of California, Berkeley, and Knowledge exchange between iHAN universities Drs Anders Rodell and Michael Gejl were hosted by Pro- In February 2014, Professors Maurice Ptito and Ron fessor David Reutens at the Center of Advanced Imaging Kupers of the University of Copenhagen visited the at the University of Queensland, Brisbane. laboratory of Professor Fahmeed Hyder at Yale University, to strengthen their collaboration and to explore their Publications of the Danish arm of iHAN in 2014 mutual interest in specific magnetic resonance technol- Andalib S, Vafaee MS, Gjedde A. Parkinson’s disease and mitochon- ogy. The goal is to facilitate transfer of expertise in this drial gene variations: A review. J Neurol Sci. 2014 Aug 7. pii: S0022- technology from QNMR Core Center at Yale to the 510X(14)00513-9. doi: 10.1016/j.jns.2014.07.067. [Epub ahead of print] Panum NMR Center at the University of Copenhagen. Review. PubMed PMID: 25151610.

Fahmeed Hyder (Yale University) also visited the BRAIN- Darusman HS, Kalliokoski O, Sajuthi D, Schapiro SJ, Gjedde A, Hau J. The lab and CEHA (UCPH) in July and October 2014. A wide success rate in a complicated spatial memory test is determined by age, range of MRI and Magnetic Resonance Spectroscopy sex, life history and search strategies in cynomolgus monkeys. In Vivo. 2014 Sep-Oct;28(5):741-50. PubMed PMID: 25189885. (MRS) methods were used successfully during these

56 · Annual Report 2014 Darusman HS, Pandelaki J, Mulyadi R, Sajuthi D, Putri IA, Kalliokoski OH, Call J, Abelson KS, Schapiro SJ, Gjedde A, Hau J. Poor memory performance in aged cynomolgus monkeys with hippocampal atrophy, depletion of amyloid beta 1-42 and accumulation of tau proteins in cerebrospinal fluid.In Vivo. 2014 Mar-Apr;28(2):173-84. PubMed PMID: 24632970.

Gjedde A. Positron emission tomography of brain glucose metabolism with [18F]fluoro-deoxyglycose in humans. In ‘Brain Energy Metabolism’, Neuromethods, 2014. Vol. 90, chapter 14. p341-364. Springer Protocols. Key persons from the InnoLife consortium after the presentation of the Lauritzen KH, Morland C, Puchades M, Holm-Hansen S, Hagelin EM, InnoLife project for the EIT Governing Board, Brussels on 9 December, Lauritzen F, Attramadal H, Storm-Mathisen J, Gjedde A, Bergersen LH. 2014. From left to right: Koenraad Debackere (Professor, KU Leuven, Lactate receptor sites link neurotransmission, neurovascular coupling, and Belgium), Lucyna Wozniac (Prorector for Research, Medical University brain energy metabolism. Cereb Cortex. 2014 Oct;24(10):2784-95. doi: of Lodz, Polen), Ursula Redeker (Spokesperson for the Board, Roche, 10.1093/cercor/bht136. Epub 2013 May 21. PubMed PMID: 23696276. Germany), Ulla Wewer (Dean, Faculty of Health and Medical Sciences at University of Copenhagen, Denmark) and Elio Riboli (Director, School of Rinholm JE, Bergersen LH. White matter lactate – does it matter? Public Health at Imperial College London). Neuroscience. 2014 Sep 12;276:109-16. doi: 10.1016/j.neuroscience.2013.10.002. Epub 2013 Oct 12PMID: 24125892 PubMed – in process. More than 50 core partners (and their 90 associate Stender J, Gosseries O, Bruno MA, Charland-Verville V, Vanhaudenhuyse A, Demertzi A, Chatelle C, Thonnard M, Thibaut A, Heine L, Soddu A, organizations), including leading businesses, public Boly M, Schnakers C, Gjedde A, Laureys S. Diagnostic precision of PET partners, research centers and universities from nine EU imaging and functional MRI in disorders of consciousness: a clinical countries, responded to the 2014 call for KICs, submit- validation study. Lancet. 2014 Aug 9;384(9942):514-22. doi: 10.1016/ S0140-6736(14)60042-8. Epub 2014 Apr 15. PubMed PMID: 24746174. ting a proposal for the project InnoLife – Healthy living and active aging. Early in December 2014, InnoLife was Stender J, Kupers R, Ptito M, Gjedde A. Unresponsive, but Aware: The designated the winning KIC, to be called EIT Health, Non-Behavioral Minimally Conscious State. Brain Disord Ther. 2014, 3:5. and was awarded approximately a business value of Stender J, Kupers R, Rodell A, Thibaut A, Chatelle C, Bruno MA, Gejl M, 395 million euros over 7-10 years. Partners in EIT Health Bernard C, Hustinx R, Laureys S, Gjedde A. Quantitative rates of brain include University of Copenhagen, University of Oxford, glucose metabolism distinguish minimally conscious from vegetative state patients. J Cereb Blood Flow Metab. 2014 Oct 8. doi: 10.1038/ Karolinska Institutet, Novo Nordisk, Abbott Laborato- jcbfm.2014.169. [Epub ahead of print] PubMed PMID: 25294128. ries (Spain), National Institute of Health and Medical Research (Inserm, France), Philips Healthcare and Roche Diagnostics GmbH (so-called core partners). The goal of the EIT Health is to promote entrepreneurship and Other international networking and events develop innovations in healthy living and active aging, providing the EU with new opportunities and resources. KIC – and the Center for Healthy Aging This will be achieved by delivering products, services and In early 2014, the European Institute of Innovation and concepts designed to improve quality of life and contrib- Technology (EIT), based in Budapest, Hungary, launched ute to the sustainability of healthcare across the EU. The a call for Knowledge and Innovation Communities (KICs), partners represent the top tier in excellence in healthcare as part of the larger European Union (EU) initiative, and research, and the outreach activities of EIT Health Horizon 2020. The goal of the KIC initiative is to provide are expected to spread throughout the EU. innovative solutions to societal problems through highly At the University of Copenhagen, the Center for integrated, creative and excellence-driven partnerships Healthy Aging (CEHA) will be the central player in the EIT among stakeholders in education, technology, research, Health. Currently, Dean Ulla Wewer is interim director of business and entrepreneurship. KICs tackle the grand- the education part of the project. challenges facing the EU, to ensure economic growth The relationship between the University of Copen- along with sustainable solutions into the 21st century. hagen and IARU is an acknowledged component of the

Annual Report 2014 · 57 KIC, opening opportunities for new and strengthened Tohoko University collaboration between CEHA, the University of Copenha- In 2012 CEHA established an agreement with the Insti- gen, IARU universities and beyond. tute of Development, Aging and Cancer (IDAC), Tohoku More information on the EIT Health KIC is available University, Japan. The objective is to promote and im- at: http://eit.europa.eu/sites/default/files/EIT Health - prove academic exchange between the two institutions. Factsheet 2014.pdf Initially, the cooperation is be focused on following fields of training and research: CEREHA 1) Molecular mechanisms of aging, In 2013, CEHA also became a partner in the Israeli Cen- 2) Genome instability and aging and, tre of Excellence for Research on Environment, Health 3) Multidisciplinary aging-related human science and and Aging (CEREHA). CEREHA is the most important technology. aging research initiative in the Galilee region of Northern Israel. MouseAge MARRIAGE CEHA is part of a European network, MouseAge, which Since 2012, CEHA has been member of the EU funded is being developed for preclinical testing of interventions Initial Training Network MARRIAGE. The overall objec- in mouse models of age and age-related diseases. tive is to provide state-of-the-art training in study of the The number of people over 65 is predicted to double biology of aging. The network includes European Aging in the next 50 years. Age is the most important risk fac- Centers and the Training Network will create a pan-Euro- tor for stroke, heart attacks, cancers, diabetes, and many pean Network focused on aging research. other chronic diseases. Tackling the effects of the aging population in Europe has stimulated funding of research ABRAHAM initiatives at both national and European levels. A key CEHA is also active in the establishment of the network requisite to develop new interventions for age-related ABRAHAM, which include researchers, companies, gov- conditions and promote healthier aging is the availability ernmental institutions and patients/citizen. The network and use of preclinical murine models. There is currently started in 2010. ABRAHAM aims to create a transat- a clear lack of such models and appropriate standard- lantic network with partners from the EU, the USA ized methodologies to test interventions. Therefore, to and Canada. This network will build on several existing improve the quality of European aging research a coor- projects, some of which involve transatlantic partner- dinated interdisciplinary action is needed to standardize ships that focus on aging-related issues, such as genome methodologies and animal welfare, and to define end- stability and metabolism and systems biology. The found- points, as well as centralizing information, models and ing partners of ABRAHAM are the University Medical technologies for the assessment of interventions. This Center Groningen (The Netherlands, EU), University of Action proposes to set-up a highly interactive and flex- Copenhagen (Denmark, EU), University of Newcastle ible European network, which will create a critical mass upon Tyne (United Kingdom, EU), Mayo Clinic (Minne- of cross-disciplinary scientists, clinicians and industrial sota, USA) and McGill University (Montreal, Canada) and partners to reach consensus on ways to test preclinical all have extensive collaborations with industries in the interventions in aging mice. It will consolidate current food, pharmaceutical and medical technology sectors. best practice across leading European institutions and ABRAHAM aims to enhance integration in the field of researchers, maximize resource efficiency, and provide a biobanking and basic aging research in order to contrib- platform to help train the next generation of scientists. ute to the goal set by the European Commission, namely adding two extra healthy years to life in 2020. www.cost.eu/COST_Actions/bmbs/Actions/BM1402

58 · Annual Report 2014 Selected educational activities

Educational activities

An important goal for CEHA is to educate the next explored this via ethnographic fieldwork at two activity generation of aging researchers. To this end, CEHA centres in the Copenhagen area, and via document stud- scientists make a concerted effort to provide high quality ies of policy papers and gerontological literature about educational resources to CEHA students/trainees, and the concept of activity. Active ageing policies can be to recruit junior and senior scientists with appropriate seen as operationalisations of knowledge forms and eve- research interests and/or expertise to the CEHA faculty. ryday life problems. Together, they are crafted into one CEHAs educational programs include undergraduate common statement: activity can unmake old age. These and graduate level courses on aging-related topics and policies constitute solid formats with specific ideals of specialties as well as opportunities for postdoctoral stud- the good late life. But when these ideals about the good ies under the mentorship of CEHA faculty. Educational late life become entangled with the everyday practices of activities increase year to year. Selected examples are the elderly, they are transformed in various ways. While described below. active ageing may constitute an unmaking of old age, this is a generative unmaking that creates new forms of Selected PhD dissertations the good late life. Below, examples of dissertations from the Themes and the Communication Platform are described. Complete lists of The influence of lifestyle interventions dissertations are available above (pp. 12, 19, 26, 35). on glucose homeostasis

Lund MT. , CEHA Theme II, University of Copenhagen, Active ageing and the unmaking of old age: April 2014. The knowledge productions, everyday practices and policies of the good late life. The aim of the thesis was to investigate the effects of years of endurance training on glucose homeostasis and Lassen AJ. CEHA Theme I, University of Copenhagen, to investigate alterations in glucose homeostasis with a September 2014. diet and subsequently a gastric bypass operation induced Since the end of the 1990s, the European Union and the weight loss. Two studies showed lower plasma glucose World Health Organization have proposed active ageing and insulin concentrations in endurance trained healthy as the best possible solution to the problem of age- young men compared with untrained men after intake ing populations. This dissertation discusses how active of liquid mixed meal, in an oral glucose tolerance test ageing policies are constructed. Aske Juul Lassen has and an intravenous glucose infusion test. After gastric

Annual Report 2014 · 61 bypass operation, improved glucose metabolism leads neuroanatomy course’), Senior Researcher Ellen Garde to remission of type 2 diabetes, but the beta cells were (Theme II) still failing , and therefore regain of weight is likely to be • Principles and confocal microscopy I and II, Associate associated with redevelopment of the disease. The stud- Professor Clara Prats (Theme II). ies are relevant for understanding the increase in type 2 • Aging skeletal muscle: size, signalling and satellite diabetes in aging populations and for evaluating physical cell, Assistant Professor Abigail Mackey (Theme III) training as a preventive measure. • Matrix biology – cell-matrix interplay, physiology and function of extracellular matrix, Associate Professor Tendon and skeletal muscle responses to immobi- Katja Heinemeier and Professor Michael Kjaer (Theme lization and rehabilitation in humans: Influence of III). aging and growth hormone administration Boesen A. CEHA Theme III, University of Copenhagen, Post graduate level April 2014. Selected examples: The aim of the study was to determine age-related differ- • Introduction to the Danish welfare model and health ences in the influence of immobilization and subsequent care system, at the study program Erasmus Mundus re-training on the connective tissue, structural and me- Master in Public Health, Associate Professor Anne- chanical properties in human skeletal muscle and tendon. grete Juul Nielsen (Theme I). Administration of GH counteracted the loss of tendon • The physical limits for you and your patient, Society stiffness in young but not in old individuals, but had no of Physician Education (LUF, Professor Flemming Dela influence upon muscle loss independent of age. The find- (Theme II). ings indicate that GH/IGF-I stimulates matrix proteins in • Symposium on CAMB, Nordic Gerontological Con- both skeletal muscle and tendon and abolishes the inac- gress, Associate Professor Rikke Lund (Theme II). tivity related loss in tendon stiffness, and thus show that • Physical training, post graduate course, The aging GH may have a matrix stabilizing effect during periods patient for young resident doctors, Nina Beyer with muscle inactivity in young but not in old individuals. (Theme III). • Biological mechanisms of aging – changes in the Unsettling successful ageing: DNA with aging, Summer School on Healthy Aging, A history and queering of the concept Professor Lene Juel Rasmussen (Theme III) of successful ageing in ageing research • Overuse injuries in the lower extremity in young and elderly, Idrottsmedicinsk Diplomkursus (Steg II) Bülow MH. CEHA Communication Platform, University i Svensk Idratsmedicinsk Selskab, Professor Michael of Copenhagen, April 2014. Kjær (Theme III). This dissertation aims to, on the one hand, map out the central themes and issues emerging in the recent histori- Master level cal discussions and practices related to the concept of Selected examples: ‘successful ageing’ within aging research, and, on the • User-driven innovation of welfare technologies for other hand, to critically engage with the norms and un- older citizens, Guest lecture at the master program IT derstandings of ‘aging’ and what might be called ‘good & Health, Aske Juul Lassen (Theme I) aging’ that this conceptual frame relates to. • Ethnology project – supervision of MA student as part of photo/sound elicitation project on retirement, PhD courses Kamilla Nørtoft (Theme I). CEHA researchers also taught or contributed at several • Health promotion in a community setting, Professor PhD courses, for example: Susan Reynolds Whyte (Theme I). • Organizing linking magnetic resonance imaging • Social relations and health, Lund Rikke (Theme II). (MRI) to the neuroanatomy of the human brain (‘MRI • Psychometrics, Erik Lykke Mortensen (Theme II).

62 · Annual Report 2014 • Gerontology – about the complex issues in dealing • Physical activity as prophylaxis and Fitness training with older patients, Charlotte Juul Nilsson (Theme II) with chronic disease, Michael Kjaer (Theme III) • Science communication and interdisciplinarity, • Mitochondria in disease and aging, Claus Desler Thomas Söderqvist, (CEHA Communication Platform). (Theme III).

Pre graduate level CEHA senior researchers also supervise students in Selected examples: bachelor and master level programs, some of whom are • Medical physiology and pathophysiology, Flemming affiliated with different departments at the University of Dela (Theme II). Copenhagen. • Psychology and health communication, Erik Lykke Mortensen (Theme II) Other dissemination activities • Social epidemiology and public health, Charlotte Juul Selected activities outside the university, such as lectures Nilsson (Theme II) and presentations at public and private hospitals, socie- • The effect of immobilization and aging on tendon ties, associations, organizations, general public, etc. are: and muscle, Peter Magnusson (Theme III). • Healthy Aging in a Community Context, presenta- • Physical activity and biochemical-physiological tion at the Vordingborg Municipality Health Center changes, Michael Kjaer (Theme III) Seminar in Stege, 23 April, Bjarke Oxlund (Theme I).

Annual Report 2014 · 63 • Formal and informal caregiver support in Denmark, • Can one run from the metabolic syndrome?, Sympo- working paper for Briefing Book for The Com- sium arranged by Astra-Zeneca for diabethologists monwealth Fund’s 17th International Symposium and diabetes nurses, Tivoli Congress Center, October, on Health Policy: “Caring for High Need/High Cost Flemming Dela (Theme II). Patients: The Test of a High Performing Health Care • Lifestyle intervention and muscle adaptation, three System”, 19-21 November, Washington D.C., Karsten lectures at the Ubberup Folk High School, 3 March, 30 Vrangbæk (Theme I). April and 19 November, Jørn Wulff Helge (Theme III). • Getting into the aging brain: does scars and shrink • Ubberup project, TV-interviews and film programs matter?, Ældre Sagen (DaneAge), Rødovre (January); on the National Channel TV2 News, 25 March and Folkeuniversitetet (Open University Denmark), Århus “Geek of the Week” on TV Lorry 10 September, Jørn (March); Forskningens Døgn (Festival of Research), Wulff Helge (Theme III). Hvidovre Hospital (April); Lions Club – Søllerød (June); • Protein intake and muscle size – for men, lectures for Inspirational Seminar for Teachers AOF, Amager (Sep- dairy and meat industry authorities, Copenhagen, tember); Opening of Senior-Academy, Skanderborg 19 September and on the annual meeting for Dan- (September); Activity Center Bakkehuset, Rudersdal ish Dairy Association, Randers, 22 May, Lars Holm Municipality (November). Ellen Garde (Theme II). (Theme III)

64 · Annual Report 2014 Selected joint activities, grants and appointments Selected joint activities, grants and appointments

Joint activities CEHA-BRIC seminars Throughout 2014, CEHA and the Biotech Research & CEHA retreat Innovation Centre (BRIC) conducted weekly research CEHA holds an annual retreat, at which CEHA scientists seminars on important topics in biological sciences. This share data, accomplishments and concerns and discuss seminar series features international speakers, who are potential areas of shared interest and opportunities for at the forefront of their respective fields, and who agree collaboration. to present seminars on research and/or technologies that In May 2014, CEHA held a retreat to identify and are having a major impact on biological and biomedical promote new interdisciplinary projects. During a morning sciences. session, presenters reviewed ongoing research, described possible new projects, and discussed the CEHA com- The 2014 CEHA-BRIC seminars included: munication strategy/platform, and the role played by • The interplay between non-coding RNA, Rapamy- management in facilitating dialogue across research cin and telomeres in cellular senescence and aging. themes and interdisciplinary research. Retreat discussions Speaker: Brian Luke, Zentrum für Molekulare Biologie were facilitated by Dr. Laura Meagher, Innogen & ISSTI, der Universität Heidelberg (ZMBH), Germany. Host: University of Edinburgh. Hocine Mankouri, CEHA. February 6, 2014 • Systemic DNA damage responses: organismal adjust- Workshop on interdisciplinary research ments to genome instability. Speaker: Björn Schu- In March 2014, Associate Professor Astrid Jespersen macher. Cologne Excellence Cluster for Cellular Stress (Theme I) organized a workshop on interdisciplinary Responses in Aging-Associated Diseases (CECAD), research in collaboration with Dr. Laura Meagher and Cologne, Germany. Host: Lene Juel Rasmussen, Dr. Catherine Lyall, University of Edinburg, at the Faculty CEHA. February 27, 2014. of Humanities, University of Copenhagen. Workshop • Sequencing of DNA template strands in single cells. participants included 45 scientists from CEHA and many Speaker: Peter M. Lansdorp, European Research In- individuals from other interdisciplinary research initia- stitute for the Biology of Ageing (ERIBA), Groningen, tives, including Governing Obesity, UNIK Food fitness Holland. Host: Ian Hickson, CEHA. March 6, 2014. and Pharma, and Counteracting Age-Related Loss of • Aging of hematopoietic stem cells. Speaker: Gerald Skeletal Muscle Mass (CALM). de Haan. European Research Institute for the Biology

66 · Annual Report 2014 of Ageing, University Medical Center Groningen, the Friday. How CEHA can help communicate your research Netherlands. Host: Lene Juel Rasmussen. October 9, to the public. CEHA Communication and Press Officer 2014. Gitte Inselmann Frandsen gave a presentation at this • Telomere functions during the cell cycle. Speaker: event. Jan Karlseder, Molecular and Cell Biology Laboratory, the Salk Institute for Biological Studies, US. Host: Ian Major grants Hickson. December 4, 2014. • Lifespan regulation via MAPK activation in C. elegans Center for Chromosome Stability DNA repair mutants. Speaker: Hilde Nilsen. Depart- Members of the Center for Healthy Aging were recently ment of Clinical Molecular Biology, University of Oslo awarded a major national research grant of 65 Mio DKK and Akershus University Hospital, Norway. Host: to establish the Center for Chromosome Stability. The Mansour Akbari. December 11, 2014. award from the Danish National Research Foundation (DNRF) was made as part of their Centers of Excel- More information: www.bric.ku.dk/seminars_events/ lence program, and will permit recruitment of two new seminars research groups from overseas. The Center for Chromo- some Stability will be directed by Professor Ian Hickson Network for Young Scholars from Theme III, and will also include Associate Professors Network for Young Scholars (NYS) was established in Andres Lopez-Contreras, Ying Liu and Hocine Mankouri 2010 by CEHA undergraduate and postdoctoral fellows as Principal Investigators (also Theme III). The mission to promote interdisciplinary research training, educa- of the new Center will be to define how structural tional activities, and improve social interactions among alterations in chromosomes affect the aging process in young CEHA researchers. Network activities are sched- humans; in particular, how they cause age-associated uled and coordinated by the NYS Steering Group, made diseases such as cancer and infertility. For example, one up of CEHA PhD and postdoctoral trainees. of the proposed new recruits, Professor Eva Hoffmann, will be investigating how genome instability affects fertil- In 2014, the NYS Steering Group members were: ity and birth defects in older mothers. • Amy Clotworthy, Postdoc (Theme I) • Michael Simon Nixon, PhD student (Theme I) Research Initiative on • Sanne Jessen, Postdoc (Theme II) Brain Barriers and Drug Delivery • Andreas Vigelsø Hansen, PhD student (Theme II) The Research Initiative on Brain Barriers and Drug Delivery • Claus Desler, Assistant Professor (Theme III) (RIBBDD) is a network of five independent research units • Jon Ambæk Duurhus, PhD student (Theme III) in four Danish universities. RIBBDD was formed in March • Thomas Lau Hansen, PhD student (Theme III) 2014 and received 40 Mio DKK funding over three years • Morten Hillgaard Bülow, Postdoc (Communication from the Lundbeck Foundation, with the possibility of two and Outreach Platform) years additional funding at the end of the initial term. The • Line Damberg, Academic Officer, CEHA Administration goal is to understand mechanisms that promote and/or regulate transport of small molecule drugs across the BBB, Activities in 2014 and cellular communication in the brain. Professor Martin The NYS Steering Group organized the IARU Graduate Lauritzen, the PI of CEHA’s Theme II (neuroscience), is Student Conference (GSC), held June 21-22, 2014. This heading the project and Agnieszka Hac-Heimburg is ad- event is described in greater detail on p. 54. ministrating its activities. For more: www.ribbdd.dk The NYS Steering Group initiated work to prepare a catalogue covering relevant PhD courses. NYS also organized a special event called Academic

Annual Report 2014 · 67 Appointment

Søren Bregenholt appointed as Honorary Industrial Ambassador In September 2014, the Faculty of Health and Medical Sciences appointed its first Honorary Industrial Am- bassador: Corporate Vice President and Head of R&D External Relations Søren Bregenholt from Novo Nordisk A/S. Søren Bregenholt is the first to hold this title, which is awarded to individuals with special relevance for faculty research and teaching, a high professional level and significant work experience. The Honorary Industrial Ambassador is expected to generate innovative new ideas and to work with students and researchers to create concrete solutions and products. Søren Bregenholt has been with Novo Nordisk A/S since 2010. Previously, he was director of the bio-tech firm Symphogen. He has more than 10 years experience in external relations, strategic partnerships and alliance management involving universities, biotech and pharmaceutical industries. Novo Nordisk A/S is Danish partner in the KIC (see p. 57).

68 · Annual Report 2014 Søren Bregenholt Photo: Novo Nordisk A/S

“Thinking about it, most modern break- deep insights that often only exist in leading through innovations are based on a formula academic laboratories. On the other side, including world class insights and inven- collaborating with industry allows academia tions, committed, talented individuals well access to translation tools, resources and direc- as organizations translating inventions into tion, often providing a clear competitive edge products for the benefit of customers. This is to academic scientists. also true for Novo Nordisk – all the way from More likely than not, such collaborations our formation in 1923 to our latest modern hinge on young, talented postdocs or jun- medicines. ior faculty staff not only being the epicentre It is clear that changing European demo- of knowledge and drive, but also building graphics impose an increasing need for new bridges between the industry and the aca- ways of allowing the population to live longer demic objectives and mindsets crucial for healthy, independent and productive lives. To mutual success. successfully bring such innovations forward As Industrial Ambassador, I am part of – be they IT solutions, medical devices, new the formula. I facilitate collaborations to medicines or whole new ways of integrating ensure a two-way exchange of knowledge and healthcare – we must commit ourselves to the value, while focusing on providing opportu- winning formula noted above. nities for the most talented students to experi- Increased industry-academia collabora- ence what industrial science is about, as they tion is the fastest way to success. Industry not will be the ones to ensure future discoveries only needs access to inventions from aca- and inventions – and their translation into demia – successful translations in innovation innovations that benefit the European popu- depend on access to models, technologies and lation.”

Annual Report 2014 · 69 70 · Annual Report 2014 Management Organization Chart

Dean

Managing International Internal Director Scientific Advisory Advisory Board Secretariat Committee

Steering Group

Theme Theme Theme Communi- Leaders Leaders Leaders cation and Outreach I II III Team

Research Groups Research Groups Research Groups Management

The management of the Center for Healthy Aging is • Professor Ian Hickson/Hocine Mankouri (Theme III) anchored at the Faculty of Health and Medical Sciences, • Professor Thomas Söderqvist (Communication and Dept. of Cellular and Molecular Medicine. CEHA admin- outreach) istrative duties are carried out by Managing Director, a Steering Committee, an International Scientific Advisory Meetings in 2014: 7 January, 4 March, 1 April, 10 June, Board and Administrative staff, with the Managing 11 September, 7 October, 4 November and 19 Decem- Director reporting to the Dean of the Faculty of Health ber. The CEHA Steering Committee also organized the and Medical Sciences, Dr. Ulla Wewer. Dr. Wewer is joint meeting with CEHA senior researchers on 6th May ultimately responsible for all CEHA activities. 2014 to acknowledge the beginning of a new funding cycle (2014-2018), but also to share ongoing research CEHA Steering Committee themes and to discuss potential future joint collabora- The CEHA Steering Committee provides oversight for tions (see p. 29-31). research activities, financial issues, recruitment, strategic planning and outreach. The Chair of the Steering International Scientific Advisory Board Committee is the Managing Director, Professor Lene Juel During 2014, the International Scientific Advisory Board Rasmussen (Theme III), and the Committee members (SAB) was appointed for the period of 2014-2018. It in- are leaders of the three research themes, as well as the cludes eight distinguished scientists, representing broad leader of the communication and outreach platform. The scientific expertise relevant to CEHA research. Committee meets approx. eight times a year. The role of the SAB is to provide advice about strategic planning, recruitment, feasibility, progress CEHA Steering Committee members: and development of the Scientific Program. The Board • Managing Director – Professor Lene Juel Rasmussen proposes criteria for evaluating scientific progress and (Chair) success, assists in establishing suitable external domestic • Assoc. Professor Astrid Pernille Jespersen (Theme I) and international collaborations, and advises on scientific • Professor Allan Krasnik (Theme I) goals. Finally, SAB helps CEHA leadership ensure that its • Professor Erik Lykke Mortensen (Theme II) research programs meet the highest international stand- • Professor Martin Lauritzen (Theme II) ards and achieve optimal scientific impact. The Board • Professor Michael Kjær (Theme III) meets once a year in Copenhagen.

Annual Report 2014 · 73 The first meeting will take place after the summer of • Prof. Vilhelm Bohr, MD DMSci, Lab Molecular Geron- 2015 in connection with the annual CEHA meeting. The tology NIA/NIH, USA (International PI, Biomedicine) program will include meetings with the Theme Leaders, • Prof. Carlos Mendes de Leon, PhD, University of discussions of scientific progress, and consultation with Michigan School of Public Health, USA, (International CEHA management. The SAB reports to Dean Ulla Wewer. PI, Epidemiology)

The SAB members are: Departmental Chairs from: • Professor Sarah Lamb, Brandeis University, US • Dept. of Neuroscience and Pharmacology • Professor Dr Ulrika Winblad, Uppsala University, Swe- • Dept. of Cellular and Molecular Medicine den • Dept. of Public Health • Professor Erik Boddeke, University of Groningen, • Dept. of Biomedical Sciences Netherlands • Professor George Brooks, University of California, Deans from: Berkeley • Faculty of Humanities, Prof. Ulf Hedetoft • Professor Boo Johansson, Göteborg University, Swe- • Faculty of Social Sciences, Assoc. Prof. Troels Øster- den gaard Sørensen • Professor Tone Tønjum, Oslo University, Norway • Professor Jan Vijg, Albert Einstein College of Medi- CEHA Administration cine, US CEHAs administrative staff manages logistics and • Dr Erinma Ochu, University of Manchester, UK helps coordinate research activities and programs. The secretariat is centrally located in the Panum Building, Internal Advisory Committee Faculty of Health and Medical Sciences. In 2014, it in- The members are: cludes three full-time employees: Tina Gottlieb, Head of • Dean of the Faculty of Health and Medical Sciences, Administration; Line Damberg, Academic Officer; Gitte Prof. Ulla Wewer MD DMSci (Chair) Inselmann Frandsen, Communication and Press Officer • Managing Director, Prof. Lene Juel Rasmussen, PhD located at the CEHA secretariat. (Vice Chair)

74 · Annual Report 2014 Selected communication and outreach activities

Selected communication and outreach activities

Events tragedy of old age’. Others are more skeptical: How about the ethical and existential consequences, not to Drawing healthy aging mention overpopulation and food crises? And is science In November, CEHA hosted the public event Drawing actually able to bring man eternal life? In the following science at the Medical Museion, Faculty of Health and debate, postdoc Morten Hillgaard Bülow from the CEHA Medical Sciences, University of Copenhagen. In a col- communication team raised the themes of ‘successful laboration between CEHA, the Danish Comics Commit- aging’ and ‘research and the pursuit of living forever’ tee and the Medical Museion, the idea was to combine with independent aging researcher Henning Kirk, phi- popular science talks with real-time cartoon drawing. losopher Søren Riis, and ordained priest Ane Mia Lykner. Four young CEHA researchers – Kamilla Nørtoft (Theme Approximately 150 people, mostly in their 30s, partici- I), Rikke Hodal Meincke (Theme II) Jakob Agergaard pated in the event. (Theme II) and Claus Desler (Theme III) – presented aspects of their research projects while cartoonists Erik ESOF 2014 and Science in the City Petri and Katrine Clante continuously annotated and The largest European science conference, ESOF, and the illustrated their presentations on a large paper roll which open science festival, Science in the City, were held in was projected onto a large screen in the background. Copenhagen 21-26 June. CEHA researchers participated The discussions continued over a glass wine in the muse- in both events. ESOF featured 120 sessions related to um’s reception room. The event attracted approximately society, policy, business, and careers in science. CEHA 100 people, primarily elderly people and students. Managing Director Lene Juel Rasmussen hosted one of the scientific sessions:Young scientists fighting age- Live forever related disease. Also in November, CEHA organized an event in col- The Science in the City festival was open to the pub- laboration with the Copenhagen International Docu- lic. More than 80 sessions in Danish and other languages mentary Film Festival (CPH:DOX) in the Koncertkirken provided the audience with a unique opportunity to event venue, Copenhagen. In the first part of event, we experience scientific research first-hand. CEHA partici- showed the documentary drama filmThe immortalists pated in the event Into the body: A journey with leading (2014). The film is about two eccentric aging research- scientists, arranged by the Faculty of Health and Medical ers, Aubrey de Grey and Bill Andrews, who strive to Sciences, University of Copenhagen. CEHA researchers achieve eternal youth in a world they call ‘blind to the Bjarke Oxlund (Theme I), Ellen Garde (Theme II), Rikke

Annual Report 2014 · 77 Lund (Theme II), and Vilhelm Bohr (Theme III) participat- Welfare Innovation Day ed in three Science Slam sessions, where they presented CEHA hosted a session entitled Active Aging – from their research in a short and precise four minute format. research to practice at the Welfare Innovation Day in A video from one the Science Slam sessions is available January 2014 in Copenhagen. The aim was to engage in at video.ku.dk/video/10096541/science-slam-aktiv- dialogue with stakeholders, especially with municipali- aldring ties. 1,300 persons participated in Welfare Innovation Day. At CEHAs session, Aske Juul Lassen (Theme I) gave Science Slam at Copenhagen Culture Night a presentation on active aging, followed by a panel The Copenhagen Culture Night (Kulturnatten), a major discussion where Allan Krasnik (Theme I), PhD student cultural event in the Greater Copenhagen region in Maja Schøler (Theme I) and Lars Holm (Theme III) gave mid-October each year, is a unique opportunity for the input and examples related to the active aging theme. University to get into dialogue with citizens. In 2014, the The Health Director of the the Ishøj Municipality, Per Faculty of Health and Medical Sciences arranged a num- Tostenæs, was interviewed about how the municipality ber of Science Slams during Kulturnatten, one of which uses its collaboration with CEHA to evaluate services for focused on aging and featured CEHA researchers Ellen senior citizens. CEHA researchers and staff also met with Garde (Theme II), Rikke Lund (Theme II) and PhD student and distributed information to event participants, before Rasmus Bechshøft (Theme III). and after the session.

78 · Annual Report 2014 CEHA on social media CEHAs social media curator, Annika Holme, is currently CEHA is active on Facebook, Twitter and Instagram, and tweeting (@sundaldring) about health and older people, uses these platforms to engage in dialogue with Danish both content generated by CEHA (e.g., press releases) citizens and other stakeholders in healthy aging. and taken from other sources. By the end of 2014 @sundaldring had 93 followers. A list of CEHA research- Facebook ers with active Twitter accounts is available at twitter. CEHAs Facebook page went online in April 2013. By the com/sundaldring/lists/sund-aldring-forskere. end of 2014, it had 10,361 likes. The page has good The most successful posts on @sundaldring include dialogue with its followers; the estimated engagement content relevant to CEHA and ongoing conversations rate (percentage of views that were shared, liked or among other Twitter consumers. The results indicate commented) is approximately 8% (an engagement rate that actively relating to the discussions on Twitter and of 1-2% is considered high). The CEHA communication relatively fast response time are important for achieving a and press officer Gitte Inselmann Frandsen is responsible ‘presence’ on Twitter. for the Facebook page and seven young CEHA researchers are part of the editorial board (www.facebook.com/ CEHA researchers communicating on Twitter sundaldring/app_208195102528120): A list of CEHA researchers with active Twitter accounts • Nanna Hilm, PhD student (Theme I) can be accessed via @sundaldring. The aims are to • Henrik Hvenegaard, Postdoc (Theme I) encourage greater use of the Twitter platform by CEHA • Jacob Agergaard, PhD student (Theme II) researchers to more widely disseminate CEHA researcher • Rikke Hodal Meincke, PhD student (Theme II) outcomes. The future main goal is that the tweeting • Andreas Vigelsø, PhD student (Theme III) CEHA researchers actively can contribute with scien- • Thomas Lau Hansen, PhD student (Theme III) tific content and debate on aging and health. Through • Morten Hillgaard Bülow, Postdoc (Communication individual researchers it will be possible to personalize team) science and show the different aspects of aging research and reach audiences interested in the various aspects of CEHAs facebook page promotes and illustrates CEHA aging research. research as well as promoting debate on aging-related topics and information/articles on aging and health from Instagram/Twitter/Facebook at Drawing Science other sources. In November, Twitter was used during the Drawing Some of the most successful updates in 2014 science event (see page 77). 51 live-tweets, including discussed the effect of arguing on health (reached highlights from the presentations and questions from the >23.000), the ability of long distance running to increase audience and the answers, got 2,839 views, the highest health span, and the effect of coconut oil on aging of view to date in a single day. One follower also posted the brain (reaching approximately 14.000 each). a question on Twitter for the researchers at the event, which was answered live by tweeting back. The use of Twitter Twitter was combined with photos on Instagram, which In July 2014, CEHA began using Twitter at the hashtag worked well. The Facebook page Sund Aldring (Healthy @sundaldring. The main goal is to stimulate interest in Aging) was also used to document the event; 1,535 fol- the public debate on healthy aging, why and how we lowers viewed the update, with an engagement rate of a should pursue it. The profile is used to: staggering 9%. • Disseminate interesting content on aging research • Ask questions related to healthy aging • Ask perspectival questions

Annual Report 2014 · 79

KEEPING ILLNESS UNIQUE KNOWLEDGE ON THE AT BAY TRAINING THAT LASTS LIFE COURSE OF THE POPULATION Basic research into cells and genes is A LIFETIME Data on thousands of middle-aged vital for understanding why frailty Many people retire directly from the Danes’ lives since birth may answer and susceptibility to disease increase office to the couch. New research some of the mysteries of aging. with age. will study which exercise habits are most lasting. PAGE 12 PAGE 16 PAGE 6

university of copenhagen

Profile / HEALTHY AGING

CEHA profile magazine Press activities A magazine containing nine articles about CEHA was CEHAs visibility in the press continues to increase with published at Welfare Innovation Day (described above). 175 articles in 2013 and 228 in 2014. During 2014, elev- The magazine is available in Danish (sundaldring.ku.dk/ en Danish and four English press releases on CEHA re- formidling/profilmagasin) and English (healthyaging. search were distributed. Two stories based on Associate ku.dk/about). Professor Rikke Lund’s research (Theme II) were among the most successful. A story on physical capacity in Book: The good senior life middle-aged individuals from different social groups was See pp 31 for details on the book ‘The good senior life’ – mentioned in the Danish National Broadcasting Radio DR a joint communication project. and the Minister of Health Nick Hækkerup commented on the results. A story on the effect of arguing on health was also popular nationally and internationally, receiving approximately 200 citations, including BBC Health. Professor Vilhelm Bohr (Theme III) published a paper indicating that coconut oil might postpose brain aging. The story based on the press release was mentioned in more than 65 international media sources, including In- dian Zee News and the American Newmax Health. Aske Juul Lassen’s PhD thesis on active aging and exercise also received a significant amount of notice.

80 · Annual Report 2014 Annual Report 2014 · 81 © Center for Healthy Aging, Copenhagen 2015. Graphic design: Signs & Wonders. Photo: Mikkel Schlosser university of copenhagen faculty of health and medical sciences center for healthy aging blegdamsvej 3b dk-2200 copenhagen n tel +45 35 32 79 00 www.sund.ku.dk www.healthyaging.ku.dk